APOE polymorphism and lipid profile in three ethnic groups in the Singapore population

Background: Serum lipid concentrations are modulated by environmental factors such as exercise, alcohol intake, smoking, obesity and dietary intake and genetic factors. Polymorphisms at the Apolipoprotein E (APOE) locus have consistently shown a significant association with total and LDL-cholesterol (LDL-C). However, their impact on HDL-cholesterol (HDL-C) may be population dependent. Having three major ethnic groups within a similar social environment allows us to study the role of genetics and their interactions with lifestyle factors on the serum lipid profile and coronary risk in Asians. Methods: This study included 1740 males (1146 Chinese, 327 Malays and 267 Asian Indians) and 1950 females (1329 Chinese, 360 Malays and 261 Asian Indians) with complete data on anthropometric indices, fasting lipids, smoking status, alcohol consumption, exercise frequency and genotype at the APOE locus. Results: Malays and Asian Indians were more obese compared with the Chinese. Smoking was uncommon in all females but Malay males had significantly higher prevalence of smokers. Malays had the highest LDL-C whilst Indians had the lowest HDL-C, The 3 allele was the most frequent allele in all three ethnic groups. Malays had the highest frequency of 4 (0.180 and 0.152) compared with Chinese (0.085 and 0.087) and Indians (0.108 and 0.075) in males and females, respectively. The 2 allele was the least common in Asian Indians. Total cholesterol (TC) and LDL-C was highest in 4 carriers and lowest in 2 carriers. The reverse was seen in HDL-C with the highest levels seen in 2 subjects. The association between ethnic group and HDL-C differed according to APOE genotype and gender. Asian Indians had the lowest HDL-C for each APOE genotype except in Asian Indian males with 2, where HDL-C concentrations were intermediate between Chinese and Malays. Conclusion: Ethnic differences in lipid profile could be explained in part by the higher prevalence of 4 in the Malays. Ethnicity may influence the association between APOE genotypes and HDL-C. APOE genotype showed no correlation with HDL-C in Malay males whereas the association in Asian Indians was particularly marked. Further studies of interactions between genes and environmental factors will contribute to the understanding of differences of coronary risk amongst ethnic groups.     

Association of TaqIB polymorphism in the cholesteryl ester transfer protein gene with plasma lipid levels in a healthy Spanish population

Genetic variants at the cholesteryl ester transfer protein (CETP) locus have been associated with CETP activity and mass, as well as plasma high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I levels. We have examined allele frequencies and lipid associations for the common CETP TaqIB polymorphism in a sample of 514 healthy subjects (231 men, mean age 37.4 years, and 283 women, mean age 35.7 years) residing in Valencia (Spain). The frequency of the less common TaqIB2 allele (0.351; 95% CI: 0.322-0. 380) was significantly lower than those reported for Northern European populations. Consistent with previous studies, we found a significant association of the TaqIB polymorphism with HDL-C levels. Homozygotes for the B1 allele had lower HDL-C levels than subjects carrying the B2 allele (P trend<0.001 and 0.002, for men and women, respectively). No statistically significant genotype effects were observed for any of the other lipid measures. Multivariate models including TaqIB genotype, body mass index, smoking, alcohol, physical activity, marital status and education were fitted to predict HDL-C levels. The TaqIB polymorphism was consistently an independent predictor of HDL-C levels (P<0.001), and explained 5.8% of its variance. To evaluate gene-environmental interactions, first order interaction terms were tested into the multivariate model. No statistically significant interactions between the TaqIB genotypes and smoking, alcohol, physical activity or education were detected. In conclusion, we observed a significant association of the TaqIB polymorphism with HDL-C levels, which remained consistent across different levels of behavioral factors. Moreover, we found that the TaqIB2 allele frequency was lower in our sample than in other European populations, which could be a contributing factor to the unexpectedly high prevalence of coronary heart disease observed in the region of Valencia.     

Environmental and genetic factors of hypertension in a biracial Beduin population.

This study attempts to understand the various factors involved in the pathophysiology of hypertension in black Beduins. Parameters known to differentiate US black from white hypertensives were examined. Sixty Beduin families (thirty families each of black and white, total of 205 subjects) were evaluated for environmental risk factors: a traditional nomad shepherd life-style compared with working in a city, living in tents or in western style housing and dietary habits related to cardiovascular risk factors. Blood pressure, body mass index (BMI), sodium-lithium counter transport rate and 24 hour urinary sodium excretion (UNa) were measured and the data obtained were compared between normotensives and hypertensives, within each racial group. The mean value of the BMI of the white population was greater than that of the black population while the BMI of hypertensives was greater than that of the normotensives in each of the racial groups. The mean systolic BP of black hypertensives was greater than that of the corresponding whites. There were no significant differences in UNa between the four groups. Sodium-lithium countertransport was significantly higher in the hypertensive whites compared with the normotensive population (0.46 versus 0.22 mmol Li efflux/IRBC/hr). The countertransport rate for black hypertensives was lower than that of white hypertensives (0.20 versus 0.46). Black families had lower socio-economic scores than did white families and families with a hypertensive member scored lower than did families with a normotensive history. These results demonstrate some similarities between the American and Beduin black hypertensive populations, in spite of entirely different life-styles, indicating that in these populations genetic factors, rather than environmental influences, appear to be dominant in the pathophysiology of hypertension.     

MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine concentrations

Background and AimDietary n-3 polyunsaturated fatty acids (PUFAs) are associated with decreased plasma homocysteine (Hcy), an important biomarker for cardiovascular disease. The S-adenosylmethionine synthetase type-1 (MAT1A), an essential enzyme in the conversion of methionine to S-adenosylmethionine, plays a key role in homocysteine metabolism. This study investigated the interaction between dietary fatty acids and MAT1A genotypes on plasma Hcy concentrations among Boston Puerto Ricans.Methods and ResultsPlasma Hcy and MAT1A genotypes were determined in 994 subjects of the Boston Puerto Rican Health Study. Dietary fatty acid intakes were assessed by interviews using a questionnaire adapted from the NCI/Block food frequency form.ResultIn the cross-sectional analysis, genetic variant MAT1A 3U1510 displayed a significant interaction with dietary n-3:n-6 PUFA ratio in determining plasma Hcy (p-value for interaction = 0.025). 3U1510G homozygotes had significantly lower plasma Hcy concentration than major allele homozygotes and heterozygotes (AA + AG) (p-value for trend = 0.019) when the n-3:n-6 ratio was >0.09. Two other MAT1A variants, d18777 and i15752, also showed significant interactions with different constituents of dietary fat influencing Hcy concentrations. Furthermore, haplotypes consisting of three variants displayed a strong interaction with n3:n6 ratio influencing Hcy concentrations.ConclusionsOur results suggest that MAT1A genotypes appear to modulate effects of dietary fat on plasma Hcy.     

Acid phosphatase, genetic polymorphism and cardiovascular risk factors in a pediatric population.

BACKGROUND: Although the clinical expression of cardiovascular disease usually occurs in adulthood, it is unanimously accepted that atherosclerosis begins in the pediatric age. Because of the early onset of the disease, it is of great importance to screen for major risk factors since pre-school age, especially in risk families. Recent investigations have shown a great interest not only in studying the classic risk factors, but also in the evaluation of oxidative stress and the main antioxidant defense systems. The major cause of this interest is the knowledge of the deleterious effect of reactive oxygen species on lipids, the endothelial membrane of arteries and, finally, on the occurrence of cardiovascular disease. POPULATION AND METHODS: 51 children of both genders, aged 9-12 years, randomly selected from a rural community, were observed. A possible association between low molecular acid phosphatase genetic polymorphism of the erythrocyte and the prooxidant status markers (epinephrine oxidase and low molecular protein phosphotyrosine phosphatase from the erythrocyte), some enzymatic systems of the body antioxidant defense (transmembranar reductase of ferricyanide and metahemoglobin reductase) and finally some intermediate phenotypes of cardiovascular disease (lipid profile and blood pressure) were studied. RESULTS: The study of prooxidant status markers and antioxidant enzymes shows significant differences for acid phosphatase and epinephrine oxidase activities in relation to low molecular acid phosphatase genetic polymorphism, the highest values observed being in those homozygous to the B allele (p < 0.05). The inter-relation study between variables showed, among other things, a significant inverse correlation between acid phosphatase and transmembrane reductase and a direct correlation between apolipoprotein B, acid phosphatase and metahemoglobin reductase. A positive family history for cardiovascular disease also showed a direct and significant correlation to total cholesterol, LDL-cholesterol and apolipoprotein B. CONCLUSIONS: The polymorphic variants of low molecular acid phosphatase and protein phosphotyrosine phosphatase with greater activity are strongly associated, not with the classic parameters of cardiovascular risk factors, but with oxidative stress indicators, such as low molecular protein phosphotyrosine phosphatase and epinephrine oxidase. Family history indicators of cardiovascular risk are clearly associated, since early ages, to some conventional risk factors, such as lipid profile and blood pressure.     

Evolution of a genetic polymorphism with climate change in a Mediterranean landscape

Many species show changes in distribution and phenotypic trait variation in response to climatic warming. Evidence of genetically based trait responses to climate change is, however, less common. Here, we detected evolutionary variation in the landscape-scale distribution of a genetically based chemical polymorphism in Mediterranean wild thyme (Thymus vulgaris) in association with modified extreme winter freezing events. By comparing current data on morph distribution with that observed in the early 1970s, we detected a significant increase in the proportion of morphs that are sensitive to winter freezing. This increase in frequency was observed in 17 of the 24 populations in which, since the 1970s, annual extreme winter freezing temperatures have risen above the thresholds that cause mortality of freezing-sensitive morphs. Our results provide an original example of rapid ongoing evolutionary change associated with relaxed selection (less extreme freezing events) on a local landscape scale. In species whose distribution and genetic variability are shaped by strong selection gradients, there may be little time lag associated with their ecological and evolutionary response to long-term environmental change.Ongoing changes in regional climates are pushing many species to shift their distribution toward higher latitudes and altitudes (1–7). Such changes in species distribution, with an expansion in previously hostile areas and contraction in areas becoming less favorable, can occur rapidly both in plants and animals (2, 3, 5, 6). As a result, major changes in community composition due to differential migration rates may occur (8). Indeed, habitat fragmentation may prevent many species from showing such a distributional response to climate change. As a result, only those species that can respond by phenotypic plasticity or genetically based local adaption will persist (9). In animal and plant species, phenotypic plasticity of phenological traits can allow individuals to adjust to climate change (1, 10, 11). In addition to changes in distribution and plasticity, an evolutionary response to climate change may occur if species evolve a genetically based adaptation to climate change (12, 13). It is important to distinguish this genetic response from a plastic response of individuals if we are to fully understand the evolutionary potential of species to evolve with climate change (14). Adaptive trait variation in relation to climate change has been shown in the classic study of Drosophila (15, 16) and in experimental and natural populations of a small number of plant species (17–20). However, in some cases, the evolutionary response to climate change may be slow due to genetic constraints (21) causing a time lag between the environmental change and an observed evolutionary response. Understanding how species track climate change by genetically based adaptive trait variation and which traits facilitate the evolution of such adaption is important; such issues determine which species may persist locally and which may shift their distribution (22, 23).In this study, we test for an evolutionary response of a genetic polymorphism in essential oil composition in Mediterranean wild thyme, Thymus vulgaris, to reduced selection associated with a warming of extreme winter freezing events over a sharp spatial climatic gradient. Our study was done in and around the Saint Martin-de-Londres basin (43°48′N, 03°46′E), which covers an area of ∼80 km² and whose southern limits are ∼20 km north of Montpellier in the Mediterranean climate region of southern France. The center of the basin (lowest altitude, 145 m) is surrounded by calcareous hills, ranging from 300 to 658 m. The study area has a Mediterranean climate with summer drought but also severe winter freezing temperatures within the basin as a result of a dramatic temperature inversion (Fig. 1). In this area, there are six different chemotypes that are the expression of a genetically controlled polymorphism in T. vulgaris (24). Two phenolic chemotypes (carvacrol and thymol) are largely dominant on the slopes outside of the basin on stony soils above 250-m elevation and four nonphenolic chemotypes (linalool, thuyanol-4, α-terpineol, and geraniol) occur within the basin below 200-m elevation on deeper, more humid soils (25–27), where they experience the winter temperature inversion. There is thus a sharp cline in chemotype frequency over only 3–5 km that goes from 100% of either phenolic or nonphenolic chemotypes to 100% of the other form, with a narrow transitional zone (Fig. 2). In short, nonphenolic chemotypes show marked adaptation to habitats, which in the past have frequently experienced extreme freezing temperatures in early winter, whereas phenolic chemotypes are sensitive to intense early-winter freezing and occur in habitats where extreme summer drought can exclude nonphenolic chemotypes (28, 29).Open in a separate windowFig. 1.Coldest annual temperature from 1955 to 2010 at the weather station of Saint Martin-de-Londres (filled squares), which occurs in the zone dominated by freezing-tolerant nonphenolic chemotypes, and from 1970 to 2010 at the Centre d''Ecologie Fonctionnelle et Evolutive–Centre National de la Recherche Scientifique experimental gardens on the northern periphery of Montpellier (open circles), where natural thyme populations are dominated by freezing-sensitive phenolic chemotypes.Open in a separate windowFig. 2.Spatial distribution and chemical composition of sampled thyme populations in the early 1970s and the 36 populations that were resampled in the present study along six transects. The chemical composition of resampled populations indicated on the map is that which was observed in the initial study. Black circles, phenolic populations; open circles, nonphenolic populations; gray circles, mixed populations. On each transect, the six populations are connected by a dashed line and are represented by a slightly larger circle than populations that were not resampled in the present study.In the part of the study area where nonphenolic chemotypes dominated populations in the early 1970s, extreme winter temperatures have become less severe (Fig. 1) with a significant increase in temperature of extreme freezing events (r = 0.36, n = 56, P < 0.01). In the 20 y before and during the initial study, winter temperatures fell below levels (−15 °C in December) that would exclude phenolic chemotypes from sites dominated by nonphenolic chemotypes (29) on five occasions. In the 16 y following the initial study, three such events were recorded. In the last 20 y, no such extreme events have been recorded in the zone dominated by nonphenolic chemotypes. The last extreme freezing event that could impact the composition of thyme populations occurred 25 y ago.Here, we test the hypothesis that phenolic chemotypes (thymol and carvacrol) now occur in sites where they were previously absent or have increased their frequency in transitional sites due to a relaxation of selection normally associated with extreme early-winter freezing temperatures. To do so, we compared the chemotype composition of populations observed in the early 1970s (26) to that in 2009–2010 for 36 populations sampled along six transects. Each transect is <10 km long, each containing six populations, with two “phenolic,” “mixed,” and “nonphenolic” populations (Fig. 2). To provide an indication of whether population-level changes are due to within-population adaptation or migration among populations, we also examine whether any increases in the abundance of phenolic chemotypes are primarily in nonphenolic or mixed populations that are spatially the closest to preexisting phenolic populations.     

Apolipoprotein E polymorphism in men and women from a Spanish population: allele frequencies and influence on plasma lipids and apolipoproteins.

The apolipoprotein (apo) E phenotype and its influence on plasma lipid and apolipoprotein levels were determined in men and women from a working population of Madrid, Spain. The relative frequencies of alleles epsilon(2), epsilon(3) and epsilon(4) for the study population (n=614) were 0.080, 0.842 and 0.078, respectively. In men, apo E polymorphism was associated with variations in plasma triglyceride and very low-density lipoprotein (VLDL) lipid levels. It was associated with the proportion of apo C-II in VLDL, and explained 5.5% of the variability in the latter parameter. In women apo E polymorphism was associated with the concentrations of plasma cholesterol and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) related variables. The allelic effects were examined taking allele epsilon(3) homozygosity as reference. In men, allele epsilon(2) significantly increased VLDL triglyceride and VLDL cholesterol concentrations, and this was accompanied by an increase of the apo C-II content in these particles. Allele epsilon(4) did not show any significant influence on men's lipoproteins. In women, allele epsilon(2) lowered LDL cholesterol and apo B levels, while allele epsilon(4) increased LDL cholesterol and decreased the concentrations of HDL cholesterol, HDL phospholipid and apo A-I. These effects were essentially maintained after excluding postmenopausal women and oral contraceptive users from the analysis. In conclusion: (1) the population of Madrid, similar to other Mediterranean populations, exhibits an underexpression of apo E4 compared to the average prevalence in Caucasians, (2) gender interacts with the effects of apo E polymorphism: in women, it influenced LDL and HDL levels, whereas in men it preferentially affected VLDL, and (3) allele epsilon(2) decreased LDL levels in women, while it increased both VLDL lipid levels and apo C-II content in men, but, in contrast to allele epsilon(4), it did not show an impact on HDL in either sex.     

遗传与环境因素对人体血浆纤维蛋白原水平的影响及临床意义

为探讨遗传与环境因素对血浆纤维蛋白原 ( Fg)的影响及临床意义 ,选择 10 5例血浆 Fg升高者 (高 Fg组 )按 1∶ 1配比设置对照 ,随访比较高 Fg(高 Fg组 )和低 Fg(低 Fg组 )患者及其一级亲属冠心病 ( CHD)发生情况。结果体重指数、高脂肪饮食、吸烟、体力活动少、高血压、甘油三酯、高密度脂蛋白、低密度脂蛋白及一级亲属血浆 Fg水平等因素进入回归方程 ;高 Fg组一级亲属 Fg水平 [( 6 .1± 0 .8g/ L) ]高于低 Fb组一级亲属 [( 4 .4±0 .5 g/ L) ];血浆 Fg浓度高者 CHD发病率 ( 2 4 % )明显高于低 Fg者 ( 10 % )。提示体重指数、高脂肪饮食、吸烟、体力活动少、高血压、甘油三酯、低密度脂蛋白与 Fg水平呈正相关 ;而高密度脂蛋白与 Fg呈负相关 ;遗传因素对 Fg有一定影响 ;Fg浓度升高是 CHD发病的独立危险因素     

Distribution and effect of apo A-IV genotype on plasma lipid and apolipoprotein levels in a Chinese population

OBJECTIVES: Hypertriglyceridaemia has been recognized as an independent risk factor for the development of coronary heart disease. Apolipoprotein A-IV (apo A-IV) plays an important role in the metabolism of TG-rich lipoproteins and HDL. However, the role of the polymorphism of the apo A-IV gene in hyperlipidaemia remains to be fully determined. The impact of the genetic variant in the apolipoprotein A-IV gene on lipid risk factor profiles for coronary heart disease was examined in Chinese patients with type-IV hyperlipoproteinaemia (HTG) and in healthy control individuals. METHODS: We genotyped five polymorphisms in the apo A-IV gene (codon 9, codon 347, codon 360, 3'end VNTR and Msp I sites) by direct sequencing or RFLP analysis in a Chinese population. RESULTS: The genotype frequencies in our results were significantly different from those reported in Caucasians. The polymorphic sites of codon 347 and codon 360, that have been widely studied in Western populations, were not observed in our population. The frequency of the G allele at codon 9 in HTG subjects was higher than that in healthy controls (P < 0.05). Serum apolipoprotein A-I (apo A-I), triglyceride (TG) and low-density lipoprotein cholesterol (LDLC) levels were affected by genotypes of codon 9, Msp I and VNTR polymorphisms, respectively, with some sex-specific effects in the control or HTG group. CONCLUSION: These results suggest that codon 9, Msp I and VNTR polymorphisms in the apo A-IV gene are associated with type-IV hyperlipoproteinaemia in a Chinese population.     

Prevalence of cardiovascular risk factors in the Spanish working population

INTRODUCTION AND OBJECTIVES: The routine medical check-up provides a good opportunity for screening workers early for cardiovascular risk factors. The aim of the present study was to investigate the prevalence of cardiovascular risk factors in the Spanish working population. METHODS: The study included 216 914 working people (mean age 36.4 years, range 16-74 years, 73.1% male) undergoing routine medical check-up, which involved a structured questionnaire, physical examination, and standard serum biochemical analysis. RESULTS: Cardiovascular disease had been diagnosed previously in 0.7% of workers, hypertension in 6.2%, diabetes in 1.2%, and dyslipidemia in 8.9%. Routine check-up showed that 49.3% (51.3% of males and 43.8% of females) were smokers, 22.1% (27.0% of males and 8.8% of females) had high blood pressure (< or =140/90 mm Hg), 15.5% (18.3% of males and 13.3% of females) were obese (body mass index > or =30), 6.2% (7.8% of males and 1.9% of females) were hyperglycemic (blood glucose >110 mg/dL), and 64.2% had dyslipidemia (total cholesterol > or =200 mg/dL, LDL cholesterol > or =160 mg/dL, triglycerides > or =200 mg/dL, or HDL cholesterol < 40 mg/dL in males or < 50 mg/dL in females). When compared with workers in the service sector and after adjustment for potential confounders, workers in manufacturing, and particularly those in construction, had higher prevalences of both high blood pressure and smoking. CONCLUSIONS: The prevalence of cardiovascular risk factors in the Spanish working population is high, particularly in males and in certain types of employment.     

Biological and genetic factors influencing plasma factor VIII levels in a healthy family population: results from the Stanislas cohort

The mechanisms underlying the variability of factor VIII (FVIII) levels are still poorly understood. The only receptor of FVIII identified so far is the lipoprotein receptor-related protein (LRP), which is thought to be involved in FVIII degradation. We aimed to characterize biological and genetic factors related to FVIII variability, focusing on coding polymorphisms of the LRP gene and polymorphisms potentially detected by molecular screening of the LRP-binding domains of the FVIII gene. Plasma FVIII coagulant activity (FVIII:C) and von Willebrand factor (VWF:Ag) antigen levels were measured in a sample of 100 healthy nuclear families (200 parents and 224 offspring). The ABO blood group and the three coding polymorphisms of the LRP gene (A217V, D2080N and C766T) were genotyped. Lipids and anthropometric factors poorly contributed to the variability of FVIII:C (<5%). A strong effect of ABO blood groups on FVIII:C levels was observed that remained significant after adjustment for VWF:Ag levels (P = 0.02). These two factors explained more than 50% of FVIII:C variability. After adjustment for VWF:Ag and ABO blood groups, a residual resemblance for FVIII:C persisted between biological relatives (rho = 0.13 +/- 0.06 between parents and offspring, rho = 0.24 +/- 0.09 between siblings) compatible with an additional genetic influence. The N allele of the LRP/D2080N polymorphism was associated with decreased levels of FVIII:C (90.4 +/- 8.7 vs. 102.2 +/- 3.5 IU/dl, P = 0.03) and VWF:Ag levels (109.1 +/- 11.2 vs. 125.4 +/- 4.4 IU/dl, P = 0.02). No polymorphism was detected in the LRP-binding domains of the FVIII gene. This study reinforces the hypothesis of a genetic influence of FVIII levels beyond the influence of VWF:Ag and ABO blood groups. The D2080N polymorphism of the LRP gene weakly contributed to the variability of FVIII:C levels in this healthy population.     

Effect of the Mediterranean diet on plasma adipokine concentrations in men with metabolic syndrome

ObjectiveWhile a Mediterranean dietary pattern (MedDiet) has been associated with favorable changes in several features of metabolic syndrome (MetS), its impact on plasma adipokine concentrations remains largely unknown. The objective of this study was to determine the impact of the MedDiet consumed under controlled feeding conditions, without (? WL) and with weight loss (+ WL), on plasma adipokine concentrations in adult men with MetS (NCEP-ATP III).Materials/MethodsThe diet of 26 men with MetS (age 24 to 62 yrs) was first standardized to a North American control diet for 5 weeks. Participants then consumed a pre-determined MedDiet for 5 weeks. Both diets were consumed under weight-maintaining isoenergetic feeding conditions. Participants then underwent a 20-week free-living caloric restriction period, after which they consumed the MedDiet again in weight stabilizing, isoenergetic feeding conditions.ResultsBody weight was reduced by 10.2% ± 2.9% and waist circumference by 8.6 ± 3.3 cm after the weight loss period and stabilization on MedDiet (P < 0.001). MedDiet ? WL had no impact on plasma concentrations of leptin, plasminogen activator inhibitor-1, resistin, visfatin, acylation stimulating protein and adiponectin. MedDiet + WL reduced plasma leptin concentrations (P < 0.01) and increased plasma adiponectin concentrations (P < 0.05) compared with the control diet and MedDiet ? WL.ConclusionData from this nutritionally controlled study suggest that short-term consumption of MedDiet has little effect on the concentrations of many adipokines in the absence of weight loss.     

中国汉族人群TRAIL基因多态性的研究

目的 探讨中国汉族人群中TRAIL基因的分布情况及其在相关疾病发生中的作用.方法 应用聚合酶链反应限制性片段长度多态性分析(PCR-RFLP)技术,对265例中国汉族人TRAIL基因第5外显子3′-非编码区1595位点(以mRNA为标准)进行检测,分析基因型频率和等位基因频率在不同性别人群中的分布.结果 Hardy-Weinberg平衡吻合度检验显示,本组各等位基因频率期望值和观察值无显著差异,且其基因多态性分布无性别差异,与日本人相比无显著差异(P>0.05),等位基因频率与非洲及美洲高加索人相比均有显著差异(P<0.05).结论 PCR-RFLP方法 检测TRAIL基因型特异性高,成熟、稳定;中国汉族人群TRAIL基因第5外显子3′-非编码区1595位点存在C/T突变.     

Study of a functional polymorphism in the p53 gene in systemic lupus erythematosus: lack of replication in a Spanish population

The aim of this study was to assess the possible association between the p53 suppressor gene codon 72 polymorphism and systemic lupus erythematosus (SLE). Our study population consisted of 513 SLE patients and 567 healthy controls. All the individuals were of Spanish Caucasian origin. Genotyping of the p53 codon 72 polymorphism was performed by allele-specific PCR. No statistically significant differences were observed between SLE patients and healthy controls when p53 codon 72 genotype and allele frequencies were compared. In addition, no evidence for association with clinical subfeatures of SLE was found. In conclusion, the p53 codon 72 polymorphism associated with SLE in a Korean population does not appear to play a major role in the susceptibility or severity of SLE in the Spanish population.     

Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: study in two Spanish populations

Background

ABCG1 mediates cellular cholesterol transport, but there is very little known about the influence of ABCG1 polymorphisms on human plasma lipoprotein cholesterol concentrations or on the interactions of these polymorphisms with diet.

Objective

Our objective was to investigate whether interactions between PUFA intake and ABCG1 polymorphisms modulate associations with plasma total cholesterol (TC), LDL- and HDL-cholesterol in two Spanish populations.

Methods

We grounded our investigation on two general population-based studies: the Hortega study (population A) and the Pizarra study (population B). Participants included 1178 individuals (50.0% women, age range 21–85 years) and 763 individuals (66% women, age range 23–73 years) from populations A and B, respectively, without lipid lowering drugs. Subjects were genotyped for ABCG1 variants. Biochemical measurements were taken by standard procedures. Dietary intakes were estimated with a validated questionnaire.

Results

In population A, the A allele homozygotes of SNP rs4148102 had higher TC and LDLc concentrations in subjects on a high PUFA diet than did the carriers of the G allele (242.1 ± 38.9 vs. 198.0 ± 36.0 mg/dL, p = 0.003, and 149.8 ± 37.9 vs. 111.4 ± 32.1 mg/dL, p = 0.005, respectively), and significant gene–diet interactions were observed (p = 0.020 and p = 0.013, respectively). In population B, similar differences in TC and LDLc concentrations were also found in association with this SNP under a high PUFA diet (253.2 ± 24.9 vs. 197.7 ± 39.9 mg/dL, p = 0.009, and 171.8 ± 20.5 vs. 120.4 ± 34.2 mg/dL, p = 0.004, respectively), but the gene–diet interactions observed were not significant (p = 0.379 and p = 0.422, respectively). In the pooled populations, differences in the TC and LDLc concentrations increased (246.8 ± 32.9 vs. 198.0 ± 37.5, p = 6 × 10⁻⁵, and 159.0 ± 32.6 vs. 114.3 ± 33.1, p = 3 × 10⁻⁵, respectively), and significant gene–diet interactions were maintained (p = 0.006 and p = 0.003, respectively).

Conclusion

In two Spanish populations, the ABCG1 polymorphism rs4148102 was associated with variations in plasma lipoprotein cholesterol concentrations in subjects with high PUFA intakes. Carriers of the AA genotype consuming high PUFA diet showed higher plasma LDLc concentrations.     

Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity,insulin sensitivity and lipid profile in the Spanish population

OBJECTIVE: To investigate the role of the Pro12Ala peroxisome proliferator-activated receptor (PPAR) gamma-2 polymorphism in the susceptibility to the insulin resistance syndrome and its metabolic complications in a population-based nationwide multicenter study in Spain. DESIGN: 464 unrelated adults (45.3% men and 54.7% women) aged between 35 and 64 years were randomly chosen from a nationwide population-based survey of obesity and related conditions including insulin resistance and cardiovascular risk factors. METHODS: Anthropometric determinations included: body mass index (BMI), waist-to-hip ratio, sagittal abdominal diameter; biochemical determinations included: fasting plasma glucose concentration and concentration 2 h after an oral glucose tolerance test (OGTT), total cholesterol, high and low density lipoprotein-cholesterol, triglycerides, leptin and insulin. Systolic and diastolic blood pressure were also measured. Genotyping of the PPARgamma-2 Pro12Ala polymorphism was determined by polymerase chain reaction and single strand conformation polymorphism analysis. RESULTS: The Ala12 allele frequency was higher in obese men than in lean men (0.15 vs 0.08, P=0.03). Men carriers of the Ala12 allele had a higher BMI than non-carriers (38.9% vs 21.3%; adjusted odds ratio 2.36, 95% confidence interval 1.10-5.05, P=0.03). However, despite higher BMI obese men carriers of the Ala12 allele had lower sagittal abdominal diameter than Pro12 homozygotes (24.1+/-3.2 vs 26.3+/-2.5 cm, P=0.01). The Ala12 allele was associated with lower total triglycerides levels in the overall population and it was also associated with lower fasting insulin levels and a higher insulin sensitivity by homeostasis model assessment (HOMA) in women. CONCLUSIONS: Our results suggest that the Pro12Ala polymorphism of the PPARgamma-2 gene promotes peripheral deposition of adipose tissue and increased insulin sensitivity for a given BMI. The results in women might be due to their different adipose tissue distribution.     

The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations

Recent data suggest that infections, inflammation and the immune system are involved in the process of atherosclerosis. The aim of the present study was to analyze the association of coronary heart disease (CHD) with three inflammation markers, C-reactive protein (CRP), serum amyloid-A (SAA) and plasma fibrinogen. The cross-sectional study included 1400 men aged 45-74 years, who participated in a cardiovascular risk factor survey in Finland in 1997. Participants with prevalent CHD had markedly higher CRP, SAA and fibrinogen levels than participants without CHD. In logistic regression models, the age, smoking, serum cholesterol and systolic blood pressure adjusted odds ratios (2nd, 3rd and 4th quartile as compared with the 1st quartile) of CHD increased gradually with increasing quartile of CRP (1.90, 2.27, 2.64), SAA (1.68, 1.83, 2.41), and fibrinogen (1.60, 1.95, 2.14). The associations weakened somewhat after further adjustment for indicators of obesity, particularly waist hip-ratio. CRP, SAA and fibrinogen levels were markedly lower among CHD patients using cholesterol-lowering medication as compared to non-users. In conclusion, CRP, SAA and fibrinogen, which are markers of inflammation, were positively and significantly associated with prevalent CHD. Central obesity needs to be considered as a confounding factor in the observed associations. These findings support the hypothesis that cholesterol-lowering drugs have an anti-inflammatory effect.     

Comprehensive evaluation of genetic and environmental factors influencing the plasma lipoprotein-associated phospholipase A2 activity in a Japanese population.

The lipoprotein-associated phospholipase A2 (Lp-PLA2) metabolizes oxidized phospholipids, generating lysophosphatidylcholine. The activity of the enzyme is known to be influenced largely by a single-nucleotide polymorphism, G994T, in the Lp-PLA2 gene. Interestingly, this polymorphism is much more prevalent in Japanese than Caucasians. The purpose of the current study was to evaluate the effects of the G994T, several environmental factors, and their interactions on the Lp-PLA2 activity in a large Japanese cohort. Participants (1,110 males and 908 females) of a health-screening examination were recruited for this study. Genotyping of the G994T was done using allele-specific polymerase chain reaction (PCR). The Lp-PLA2 activity was measured using commercial kits. The minor allele (994T) frequency of the polymorphism was 0.17 in this study, which was consistent with previous reports. According to the multivariate linear regression analysis, the G994T was the most potent factor influencing the enzyme activity (standardized beta=0.76), followed by the low-density lipoprotein cholesterol (LDL-C) level (standardized beta=0.32) and the sex (standardized beta=0.13). The LDL-C level showed a significant interaction with the G994T genotype. By contrast, no significant interaction was observed between the LDL-C level and the sex. These observations should provide useful information for future clinical and epidemiological evaluations of the Lp-PLA2 activity in cardiovascular diseases in Japanese.     

A functional polymorphism of the NFKB1 promoter is not associated with ulcerative colitis in a Spanish population

BACKGROUND: This study investigated the influence of the NFKB1-94ins/delATTG in the susceptibility/phenotype to ulcerative colitis. METHODS: We analyzed the distribution of -94ins/delATTG NFKB1 in 258 patients and 264 healthy controls from southern Spain by a polymerase chain reaction-fluorescent method. RESULTS: The genotype and allele frequencies of -94ins/delATTG did not significantly differ between patients and controls. In fact, the frequency of the -94delATTG allele was almost identical in both groups (34.8% and 35.4%, respectively), and the del/del genotype was underrepresented in UC patients (11.2% versus 14%). In addition, no association of this polymorphism was found with any of the clinical parameters analyzed. CONCLUSION: These results suggest that the NFKB1 -94ins/delATTG gene variation, previously associated with UC susceptibility in North Americans, does not influence either susceptibility or phenotype of UC in the Spanish population.