24 bp duplication of CHIT1 gene is not correlated with coronary artery disease in Corsica Island (France)

In this study we analyzed allele and genotype distributions of 24 bp duplication of the CHIT1 gene in a sample of patients (N=300) with coronary artery disease (CAD) and in a control group (N=300) from central Corsica (France), with the aim to investigate the possible association between CHIT1 genotypes and CAD in Corsican population. Serum chitotriosidase activity is increased in individuals experiencing an ischemic stroke of atherothrombotic etiology and in subjects with ischemic heart disease. Our results suggest that 24 bp duplication of CHIT1 gene is not correlated with CAD in Corsican population, according to a previous study carried out on a Spanish sample. Gene prevalence and perhaps gene-disease associations vary according to ethnicity. Further studies, based on different ethnic groups, could be suitable to determine the implication of this polymorphism with respect to CAD.     

Angiotensin-I-converting enzyme (ACE) insertion/deletion polymorphism in Mexican patients with coronary artery disease. Association with the disease but not with lipid levels

Angiotensin-I-converting enzyme (ACE) insertion/deletion (ID) polymorphism has been associated with the genetic susceptibility to coronary artery disease (CAD) and also with the lipid profile in several populations. In the present work, we analyzed the distribution of ID polymorphism in 147 Mexican patients with CAD and 100 unrelated healthy controls. The correlation of this polymorphism with the lipid profile (cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides) in the patients group was determined. Increased frequency of D allele as well as DD genotype and decreased frequency of I allele and II genotype were found in CAD patients group (pC = 0.00058, OR = 1.96, pC = 0.021, OR = 2.5 and pC = 0.00058, OR = 0.51, pC = 0.0028, OR = 0.38). Correlation between ID genotypes and lipid profile in patients was carried out in total population and separately for females and males. After they had been adjusted for age, sex and BMI, there was no association among the three genotypes (II, ID and DD) and lipids and lipoproteins in none of the studied groups. Our data suggest that genetic variation at the ACE is a genetic factor related with the susceptibility to coronary artery disease in the Mexican Mestizo population.     

Prevalence of genetic risk factors for coronary artery disease in Corsica island (France)

We have investigated the frequencies of seven markers among 100 unrelated individuals with angiographically documented CAD (Coronary Artery Disease) and among 100 unrelated healthy blood donors in the central region of Corsica island (France). The seven polymorphisms analyzed were chosen from six candidate genes involved in (1) Renin-Angiotensin system: Angiotensin converting enzyme (ACE I/D), (2) Lipid metabolism: Cholesterol Ester Transfer Protein gene (CETP TAQ1B), (3) Platelet aggregation: alpha and beta subunits of the platelet GpIIb/GpIIIa integrin complex (GpIIb HPA3 and GpIIIa Pl(A1/A2)), (4) Coagulation fibrinolysis: Plasminogen Activator Tissue (PLAT TPA25 I/D) and Methylenetetrahydrofolate Reductase (MTHFR C677T and A1298C). The samples were genotyped using the polymerase chain reaction followed by restriction enzyme analysis for the RFLPs. No significant difference in allele frequencies between patient and control groups was observed. The occurrence of the MTHFR T677T genotype and of the T677T/A1298A compound genotype is higher in cases (20%) than in the controls (4%). Odds ratio seems to indicate that individuals with the MTHFR T677T genotype and the T677T/A1298A compound genotype had a 6-fold increased risk for developing CAD (ORs = 6; 95% CIs = 1.96-18.28) suggesting a possible association of MTHFR C677T with the risk of CAD in Corsican population.     

Cholesterol ester transfer protein,apolipoprotein E and lipoprotein lipase genotypes in patients with coronary artery disease in the Turkish population

The aim of this study was to compare patients with coronary artery disease (CAD) to healthy objects, in order to explore a possible association between CAD and the variants in the gene encoding cholesterol ester transfer protein (CETP), apolipoprotein E (Apo E) and lipoprotein lipase (LPL). The relationship between CETP MspI, apo E and LPL PvuII gene polymorphisms and serum lipids were investigated in 173 patients with CAD and 111 healthy controls. The frequency of Apo epsilon4 (p < 0.05) and CETP M1 (p < 0.01) alleles were higher in the CAD group than in the control group. In the CAD group, those with the Msp M1 allele had higher levels of total cholesterol (TC) (p = 0026) and low-density lipoprotein cholesterol (LDL-C) than those with the Msp M2 allele. Subjects with an epsilon2 allele had the lowest levels of TC and LDL-C, while subjects with the epsilon4 allele had the highest. In the control group, CETP, the Msp M2 allele was associated with a higher level of high-density lipoprotein cholesterol (HDL-C) (p = 0.012) than the Msp M1 allele. The distributions of LPL genotype and allele did not differ between the CAD and control groups. The present study demonstrates that the CETP Msp1 and Apo E gene polymorphisms are associated with variations in lipids in patients with CAD and healthy controls in Turkish population.     

Haplotype analyses of cholesteryl ester transfer protein gene promoter: a clue to an unsolved mystery of<Emphasis Type="Italic"> Taq</Emphasis>IB polymorphism

Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to triglyceride-rich lipoproteins. TaqIB polymorphism (B2 allele) identified in intron 1 is associated with lower plasma CETP concentrations and higher HDL cholesterol levels and may play an antiatherogenic role in humans. However, its molecular mechanism remains unclear. To evaluate the association between the promoter polymorphisms and CETP/HDL cholesterol levels, ten novel and three previously reported polymorphisms located within 3.3 kb of the CETP gene promoter were investigated in a sample of 357 elderly Japanese men. All the promoter polymorphisms were in linkage disequilibrium with each other and with TaqIB. The -2505A allele, the "S" allele of the [gaaa](n) repeat ("S" denotes [gaaa](n)=329 bp and longer, "L" denotes >329 bp) and TaqIB2 allele were significantly associated with both lower plasma CETP concentrations and higher HDL cholesterol levels whereas -971G/A and -629A/C were significantly associated with CETP concentrations but not with HDL-C levels. The 12-polymorphism haplotypes consisting of -2804, -2505, [gaaa](n), -1930, -1674, -1129, -1046, -971, -875, -827, -629, and TaqIB were analyzed. These 12 polymorphisms generated eight main haplotypes, accounting for 86% of the observed haplotypes. The G/A/S/T/T/C/T/A/C/C/A/B2 haplotype was significantly associated with lower CETP concentrations (2.0+/-0.6 micro g/ml) and higher HDL cholesterol levels (55.1+/-12.7 mg/dl) than the other seven main haplotypes. The 5- and 3-polymorphism haplotype analyses consisting of -2505 and the [gaaa](n) repeat indicated the -2505C/A polymorphism might explain the variation in the CETP concentrations best, and the [gaaa](n) repeat and/or the -2505C/A polymorphism may independently determine the variation in HDL cholesterol levels, whereas the -629A/C and TaqIB polymorphisms were not instrumental in determining CETP concentrations as well as HDL cholesterol levels, although the latter has been frequently examined in many association studies.     

The association of cholesteryl ester transfer protein polymorphism with high-density lipoprotein cholesterol and coronary artery disease in Koreans

Cholesteryl ester transfer protein (CETP) is a key protein involved in high-density lipoprotein cholesterol (HDL-C) metabolism. It is known to affect plasma HDL-C levels, and its genetic regulation may be involved in the development of coronary artery disease (CAD). The aim of this study was to determine the frequency of the CETP Taq1B polymorphism in Koreans, and to investigate its relationship with plasma HDL-C levels and CAD. One-hundred and nineteen patients with significant CAD and 106 controls were examined with respect to their genotypes, lipid profiles and other risk factors of CAD. The genotype frequencies of B1B1:B1B2:B2B2 in males and females were 35.5%:50%:14.5% and 34.7%:42.6%:22.7%, respectively, which is comparable to previous reports in other ethnic groups. The B1B1 homozygote was associated with significantly lower HDL-C levels in females (p = 0.049) and non-smoking males (p = 0.037). After controlling for gender, body mass index (BMI) and smoking, the TaqIB polymorphism was still significantly associated with HDL-C levels (p = 0.046) and explained 5.4% of the HDL-C variation in this study. By univariate analysis, the B1B1 homozygote was a significant predictor of CAD (p = 0.043), and this was confirmed by multivariate analysis with traditional risk factors, i.e. the B1B1 homozygote was an independent predictor of CAD (p = 0.026, odds ratio = 1.97, 95% confidence interval: 1.08-3.57). In conclusion, the B1B1 homozygote of the CETP Taq1B polymorphism is associated with low HDL-C levels in females and non-smoking males, and may be an independent genetic risk factor of CAD in the Korean population.     

Lack of genetic association of cholesteryl ester transfer protein polymorphisms with late onset Alzheimers disease

Dysregulation of cholesterol homeostasis may be associated with the pathogenesis of coronary artery disease (CAD) and Alzheimers disease (AD). Recently, several single nucleotide polymorphisms (SNPs) in cholesteryl ester transfer protein (CETP) were associated with altered plasma CETP concentrations, cholesterol concentrations and CAD. Hence, these CETP SNPs represent excellent candidates for evaluating association with AD. To date, one study has evaluated the association between a single CETP SNP and AD. In this study, we examined three CETP SNPs to evaluate the genetic association of CETP with late onset AD on two study cohorts: the Religious Orders Study (ROS) series, including 85 AD and 70 non-AD individuals, and the University of Kentucky (UKY) series, including 78 AD and 84 non-AD individuals. Significant association between CETP genotypes or haplotypes and late onset AD was not detected in these two study cohorts. Moreover, the CETP genotypes and haplotypes were not significantly associated with AD when the populations were stratified for the presence or absence of apolipoprotein E4 (apoE4). In summary, CETP genetic variants were not associated with AD in two series.     

Haplotype analysis of the CETP gene: not TaqIB,but the closely linked -629C-->A polymorphism and a novel promoter variant are independently associated with CETP concentration

The TaqIB polymorphism in intron 1 of the cholesteryl ester transfer protein (CETP) gene is associated with plasma CETP concentration, high-density lipoprotein cholesterol (HDL-C) and coronary artery disease (CAD). These associations are generally thought to arise from linkage disequilibrium between TaqIB and (an)other functional polymorphism(s). To identify putative functional sites, we investigated phenotypic associations of TaqIB and four tightly linked polymorphisms (novel -2708G-->A and +784CCC-->A, and previously identified -971G-->A and -629C-->A) in 709 males with CAD (REGRESS). In addition to genotype analyses, a novel method to estimate haplotype effects was used to examine the individual and joint effects of these DNA variants on CETP concentration and HDL-C. All polymorphisms were associated with CETP concentration and HDL-C, except for -971 with HDL-C. Stepwise regression and haplotype analyses indicated that only -629 was independently associated with HDL-C. Similar analyses additionally indicated that -2708 and -629 were independently associated with CETP concentration, whereby the most frequent alleles acted in a cumulative manner. Nonetheless, detailed haplotype analysis revealed that a 3-polymorphism haplotype model consisting of -2708, -629 and -971 explained the variation in CETP concentration best. The involvement of -971 could be due to interaction effects that were observed between -971 and both -629 (P<0.001) and -2708 (P=0.047). In conclusion, the TaqIB polymorphism is not instrumental in determining CETP or HDL-C levels, but is a marker for the -629 promoter variant. Our analyses, furthermore, indicate that the -2708 and -971 polymorphisms are likely to play a role in determining CETP concentration.     

Risk factors for atherosclerotic vascular disease in patients on maintenance hemodialysis--with especial respect to reverse cholesterol transport system and hyperhomocysteinemia

Hemodialysis (HD) patients have a high mortality rate due to vascular disease (VD). Therefore, we investigated the effect of uremic dyslipidemia on VD in HD patients, with special consideration of the reverse cholesterol transport (RCT) system including high-density-lipoprotein cholesterol (HDL-C), cholesteryl ester transfer protein (CETP) and its genetic (D442G) mutation. In 414 HD patients, a sub-median HDL-C level (< 48 mg/dl) was an independent risk factor for VD. In the lower HDL-C status, the CETP mutation leading to CETP levels was independently associated with VD. In 210 selected patients, the CETP level was an independent protective factor against VD among those with higher HDL-C levels (> 45 mg/dl). We also measured serum homocysteine (Hcy) levels and examined its association with VD considering that hyperhomocysteinemia is a newly identified risk factor for atheroma. HD Patients (n = 545) had about 3 times the Hcy levels of the general population. A common C677T mutation in the gene of methylenetetrahydrofolate reductase (MTHFR) involved in Hcy metabolism was independently and directly related to serum Hcy levels with TT genotype patients having the highest levels. Patients with the TT genotype were younger and had a shorter duration of dialysis than those with the CT or CC genotype after adjustment for age at the initiation of dialysis, although there was no difference in VD prevalence among the genotypes and no association between Hcy levels and VD prevalence. In conclusion, lower HDL-C and CETP status was a risk factor for VD in HD patients, suggesting the importance of RCT. Serum Hcy levels were markedly increased in HD patients and the TT genotype may be associated with higher mortality. However, a large-scale prospective study is required to clarify whether hyperhomocysteinemia or the TT genotype is a VD risk factor among HD patients.     

Lack of association of the common TaqIB polymorphism in the cholesteryl ester transfer protein gene with angiographically assessed coronary atherosclerosis

The anti-atherogenic effect of cholesteryl ester transfer protein (CETP) genetic variants associated with lowered enzyme activity is controversial. Moreover, in a few studies, this effect has been evaluated in the presence of a certain risk factor constellation. We addressed this issue in a case-control study, where 415 subjects with angiographically documented coronary artery disease (CAD +), 397 subjects without CAD (in 215, CAD was excluded by coronarography (CAD-)), and 188 healthy population controls, were screened for the CETP TaqIB polymorphism. The prevalence of the low-activity TaqIB2 allele was 0.396 in CAD+, and 0.428 and 0.416 in CAD- and population controls, respectively (p = 0.40). Its presence was significantly associated with increased high-density lipoprotein cholesterol (HDL-C) in population controls (1.40 +/- 0.40 mmol/l in B1B1, 1.52 +/- 0.39 mmol/l in B1B2 and 1.58 + 0.46 mmol/l in B2B2; p < 0.03 for trend), but not in the other groups. The CETP TaqIB polymorphism accounted for < 1% of the HDL-C variance in the whole cohort (p = 0.048). After adjustment for other risk factors, the CETP TaqIB2 allele was found not to be associated with significant changes in CAD risk independently of an assumed either dominant (odds ratio (OR) 0.97; 95% confidence interval (CI) 0.66-1.44; p = 0.89) or recessive effect (OR 0.68; 95% CI 0.42-1.12; p = 0.13). The CETP TaqIB polymorphism did not show a significant interaction with other risk factors in influencing CAD risk. Our findings do not support the hypothesis that a genetic variant resulting in lowered CETP activity is associated with reduced risk of coronary atherosclerosis.     

The two novel CETP mutations Gln87X and Gln165X in a compound heterozygous state are associated with marked hyperalphalipoproteinemia and absence of significant coronary artery disease

High levels of high-density lipoprotein cholesterol (HDL-C) occur with cholesteryl ester transfer protein (CETP) deficiency. However, the extent to which CETP deficiency states may be associated with protection against coronary artery disease (CAD) has been controversial. We evaluated a Greek pedigree with high levels of HDL-C and no history of premature CAD. The proband, a 45-year-old male with an HDL-C of 194 mg/dl with absent CETP activity, was heterozygous for two novel CETP mutations (Q87X and Q165X). A 64-slice multidetector CT scan revealed minimal (<10%) narrowing of the proximal left anterior descending artery without any other evidence of coronary atherosclerosis. In contrast to previous studies, these data suggest that complete CETP deficiency does not promote premature atherosclerosis. However, it remains unclear as to whether the relative lack of coronary atherosclerosis was the direct consequence of CETP deficiency and/or the lack of traditional CAD risk factors.     

Genetic and environmental determinants of plasma high density lipoprotein cholesterol and apolipoprotein AI concentrations in healthy middle-aged men

The effects of common variants of cholesteryl ester transfer protein ( CETP ) ( Taq IB), hepatic lipase ( HL ) (−514C>T), lipoprotein lipase ( LPL ) (S447X) and lecithin cholesterol acyl transferase ( LCAT ) (S208T) on the determination of high density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (apoAI) levels were examined in 2773 healthy middle-aged men participating in the second Northwick Park Heart Study. The extent of gene:gene, gene:smoking and gene:alcohol interactions were determined. For HDL-C levels, only CETP genotype was associated with significant effects ( p <0·0001), with the B2 allele being associated with higher levels in both smokers and non-smokers. This interaction was significant at the lowest tertile of TG, suggesting that TG levels were rate limiting. As previously reported, CETP , LPL and HL genotypes were all associated with significant effects on apoAI levels (all p <0·01), with carriers of the rare alleles having higher levels and with no evidence of heterogeneity of effects in smokers and non-smokers. LCAT genotype was not associated with significant effects on either trait. There was no significant interaction between any of the genotypes and alcohol consumption on either HDL-C or apoAI levels. All genotypic effects were additive for HDL-C and apoAI. Environmental and TG levels explained more than 20% and 5·5% of the variance in HDL-C and apoAI, respectively. The novel aspect of this finding is that genetic variation at these loci explained in total only 2·5% of the variance in HDL-C and 1·89% of the variance in apoAI levels. Thus despite the key roles played by these enzymes in HDL metabolism, variation at these loci, at least as detected by these common genotypes, contributes minimally to the variance in HDL-C and apoAI levels in healthy men, highlighting the polygenic and multifactorial control of HDL-C.     

Genetic contributions to quantitative lipoprotein traits associated with coronary artery disease: Analysis of a large pedigree from the Bogalusa heart study

A pedigree of a large family with high prevalence of heart disease is subjected to association and sib-pair linkage analysis to investigate the role of 5 candidate genes in the regulation of lipoprotein metabolism and the development of coronary artery disease. At the 5% nominal significance level, the apolipoprotien B locus (APOB) was found to be linked to high-density lipoprotein cholestrol level (HDL-C), low-density lipoprotein cholestrol level (LDL-C), the ratio HDL-C/LDL-C, and apolipoprotein AI level times this ratio (apoAI × LDL-C/HDL-C). APOB (PvuII) was strongly associated with apolipoprotein B levels (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly significant association between allele 7 and low triglyceride levels (P = 0.004). No significant linkage results were found with cholesterol ester transfer protein (CETP). At the 1% nominal significance level, CETP [TaqI(B)] showed significant association with LDL-C, apoB, and HDL-C/LDL-C. There was significant linkage of lipoprotein lipase (LPL) with very-low-density lipoprotein cholestrol and the ratio apoAI/HDL-C, and strong association results between LPL (HindIII) and triglyceride levels (P = 0.005). At the 5% nominal significance level, haptoglobin (HPA) was associated with HDL-C, HDL-C/LDL-C, apoAI/HDL-C and apoAI × LDL-C/HDL-C. The apolipoprotein AI locus did not show any significant linkages or associations. The study thus indicated that genetic variation of APOB, LPL, CETP, and lecithin cholestrol acyl transferase (which is linked to HPA and CETP) may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary artery disease. © 1993 Wiley-Liss, Inc.     

An interaction between the TaqIB polymorphism of cholesterol ester transfer protein and smoking is associated with changes in plasma high-density lipoprotein cholesterol levels in Turks

Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for atherosclerosis. We investigated the effects of the TaqIB polymorphism of cholesterol ester transfer protein (CETP) on CETP activity and plasma HDL-C levels in random nondiabetic and self-reported diabetic subjects in a population with very low HDL-C levels. The rare B2B2 genotype was associated with significantly higher HDL-C levels and lower CETP activity in random subjects and with higher HDL-C in diabetic subjects. After stratification of random subjects by smoking status, the common B1B1 genotype was associated with lower HDL-C levels than the B2B2 genotype. Although smoking was associated with lower HDL-C, especially in men, HDL-C levels between smokers and nonsmokers were not different in subjects with the B1B2 or B2B2 genotypes. However, smoking (20+ cigarettes/day) was associated with a marked reduction in HDL-C in the B1B1 subjects. The B1B1/smoking interaction was not reflected in a difference in CETP activity. High triglycerides and elevated body mass index (BMI) lower HDL-C. The B2B2 genotype was associated with the highest HDL-C levels, and these levels were significantly lower in the hypertriglyceridemic subjects (>or=50th percentile). The lowest HDL-C levels were seen in hypertriglyceridemic subjects with the B1B1 genotype. Although BMI (>or=50th vs<50th percentile) did not affect HDL-C in B2B2 subjects, a high BMI was associated with markedly lower HDL-C in B1B1 subjects. Thus, HDL-C levels in Turks may be modulated by an interaction between the CETP TaqIB polymorphism and smoking, as well as an interaction with hypertriglyceridemia and BMI.     

Association between -250G/A polymorphism of the hepatic lipase gene promoter and coronary artery disease and HDL-C levels in a Southern Brazilian population

Hepatic lipase (HL) is a glycoprotein that plays a major role in remodeling high-density lipoprotein (HDL). The effect of the -250G/A promoter polymorphism on coronary artery disease (CAD) and lipid levels was studied in 231 male CAD patients and in a population-based sample of men and women (n = 514). A sample of 140 men was chosen among those included in the population-based sample as controls for the CAD sample. In the total group of CAD patients, the frequency of the -250A allele was somewhat lower (25% in CAD patients and 32% in controls; p = 0.06), but when the control samples were compared only with the CAD(+) sample (more than 60% of luminal stenosis in at least one coronary artery or major branch segment) the -250A allele was significantly less frequent (23% in the patients vs 32% in controls; p = 0.02). A multiple logistic regression analysis showed that this association was independent of classical CAD risk factors [odds ratio (OR) = 1.79, p = 0.025]. Using multiple linear regression analyses, it has been shown that this polymorphism was a significant factor affecting HDL-C levels in men from the population-based sample (p = 0.001), an interaction between -250G/A variant and wine consumption was also detected (p = 0.001). Thus, our results show that the -250G/A polymorphism in the HL gene is associated with significant variations in HDL-C levels and CAD risk in males.     

TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular disease in statin-treated patients with familial hypercholesterolemia

The effects of TaqI restriction fragment length polymorphism of the CETP gene on the occurrence of cardiovascular disease (CVD) events were investigated in patients with familial hypercholesterolemia (FH). A total of 300 FH patients, of which 116 (39%) had CVD at the start of the study, were treated with statins during a mean period of 8.5 years. The distribution of Taq1B genotypes was 31% B1B1, 49% B1B2, and 20% B2B2. No differences were found at baseline between the three genotypes, except for an association of the B1 allele with lower high-density lipoprotein (HDL)-cholesterol levels (P=0.003). All patients were put on statins within 6-8 weeks after the first visit; about 60% received simvastatin (20-40 mg daily) and 40% either pravastatin (40 mg daily) or atorvastatin (20-40 mg daily). The different statin treatments were similar for all groups. The mean change of plasma HDL-cholesterol, low-density lipoprotein-cholesterol, and triglyceride concentration during statin therapy was similar for the three genotypes. During follow-up, new CVD events were recorded in 22 (37%) of the B2B2 patients (n=59) and in 67 (28%) of B1 allele carriers (n=241) (P=0.36). The relative risk for CVD events, after adjustment for age, gender, and CVD at intake, was 1.8 (CI: 1.1-3.0) for B2B2 carriers compared to B1 allele carriers. The Taq1B polymorphism is a significant predictor of future CVD events in statin-treated patients with FH. In spite of similar improvement of the lipoprotein profile during statin therapy, our FH patients with the B2B2 genotype may have a higher CVD risk in comparison with the B1 allele carriers.     

汉族人群IL10基因多态性与血脂水平的关系

目的探讨正常汉族人群白细胞介素10（interleukin 10，IL10）基因多态性与血脂水平的关系。方法应用PCR限制性片段长度多态性分析法，检测200名汉族正常人IL10基因启动子区的3个多态位点-1082、-819和-592的各种基因型的分布，并分析它们与血清脂蛋白浓度相应的关系。结果IL10—592（AA、CA、CC）和-819位点（CC、CT、TT）各基因型间的血脂水平的差异无统计学意义（P〉0．05）；IL-10—1082位点，GA基因型与从型相比，高密度脂蛋白浓度显著增高[（1．514±0．501）mmol／LVS．（1．261±0．346）mmol／L，t=-2．225，P=0．028]，甘油三酯浓度降低[（1．701±1．836）mmol／LV8．（0．981±0．314）mmol／L，Z=-2．096，P=0．036]，但总胆固醇、极低密度脂蛋白、低密度脂蛋白血清浓度间差异无统计学意义。结论 IL-10启动区-1082位点G／A基因多态性与血清甘油三酯及高密度脂蛋白浓度相关。     

雌激素受体α基因Pvu Ⅱ和Xba Ⅰ酶切多态性与冠心病相关性

目的 探讨中国人群中雌激素受体(ER)α基因Pvu Ⅱ和Xba Ⅰ酶切多态性与冠心病(CAD)的相关性.方法 将2004年4月至2006年12月在中山大学附属第五医院心内科住院的中国南方汉族CAD患者236例为病例组,117例选自健康体检者或同期在我院住院的非CAD患者为对照组,应用聚合酶链反应-限制片断长度多态性(PCR-RFLP)分析的方法,检测CAD组和对照组的ERα基因型,比较其与相关指标的关系.结果 ERα酶切多态性分析结果显示Pvu Ⅱ存在PP、Pp、pp 3种基因型;Xba Ⅰ酶切也可区分出XX、Xx、xx 3型.Pvu Ⅱ多态性中,CAD组P等位基因型频率也显著高于对照组[42.2%(199/472)比33.8%(79/234),P=0.032],pp基因型的高密度脂蛋白水平显著高于P等位基因携带者,两组之间基因型分布差异具有统计学意义(P=0.041),X等位基因在对照组和CAD组分别为16.5%(78/472)和16.2%(38/234),两组基因型和等位基因频率差异均无统计学意义.结论 中国南方汉族人群中ERαPvu Ⅱ酶切多态性与CAD有关,P等位基因可能是CAD独立遗传危险因素;ERα Xba Ⅰ酶切多态性与CAD未发现相关.     

银杏提取物治疗血管成形术后再狭窄的机制研究

目的:观察银杏提取物(GBE)对血管成形术后血管内皮损伤再狭窄的作用,并探讨其可能机制。方法:40只兔建立髂动脉粥样硬化性狭窄模型后,随机分为4组灌胃治疗(n均=10):(1)模型对照组,于经皮经腔血管成形术(PTA)后给予生理盐水;(2)低剂量组,给予PTA兔GBE0.16g/kg/日;(3)中剂量组,给予PTA兔GBE0.32g/kg/日;(4)高剂量组,给予PTA兔GBE0.48g/kg/日;另10只实验兔普通食料喂养作为空白对照组。4周后检测各组动物血清低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)、总胆固醇(TC)、血小板活化因子(PAF)、超氧化物歧化酶(SOD)、脂质过氧化物(LPO)、丙二醛(MDA)水平以及组织c-sis基因和c-myc蛋白表达。结果:与空白对照组比较,模型对照组的血清学指标有显著差异(P<0.05)。与模型对照组相比,各实验组血清LDL-C、TC、LPO、MDA、PAF水平,组织c-sis基因和c-myc蛋白表达均明显下降(P<0.05),而HDL-C、SOD水平明显升高(P<0.05)。中剂量组和高剂量组之间所有血清学指标以及c-myc蛋白表达的差异无显著性(P>0.05),但较低剂量组明显改善(P<0.05)。三个实验组c-sis基因的差异无显著性(P>0.05)。结论:GBE可以有效防止PTA后再狭窄,其机制可能与拮抗PAF、清除自由基、降低血清脂质水平以及抑制c-sis基因和c-myc蛋白表达有关。     

β2肾上腺素能受体基因+491C/T多态性与新疆哈萨克族人血脂的关系

目的:研究β2肾上腺素能受体（β2-AR）基因+491C/T多态性在新疆哈萨克族人群中的分布及其与甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL－C）、低密度脂蛋白（LDL-C）的关系。方法: 采用横断面调查方法采集528例30 -60岁哈萨克族人的遗传标本，采用酚/氯仿法提取外周血白细胞基因组DNA，应用PCR－RFLP技术，检测β2-AR基因+491C/T基因型，分析基因型及等位基因在该人群中的分布频率及其与TG、TC、HDL-C、LDL-C水平的关系。结果:该人群β2-AR基因+491C/T位点检测出两种基因型CC、CT,分布频率分别为98.86%、1.14%，等位基因C、T频率为99.43％、0.57％，符合Hardy-Weinberg平衡(χ2=0.017, P=0.896)。两种基因型间TC、LDL-C水平有增高趋势，但差异无统计学意义；在女性中CT基因型携带者血清LDL-C水平明显高于CC基因型，差异有统计学意义（P＝0.038）；按WH01997血脂防治建议标准分类后，CT基因型、T等位基因频率与高LDL－C相关（P＝0.031）。结论:新疆哈萨克人群存在β2-AR 基因+491C/T多态性，该人群尤其是女性中CT型携带者血清LDL-C水平明显增高，CT基因型、T等位基因频率与高LDL-C水平相关，提示该多态性可能是哈萨克人群尤其是女性的高LDL-C的易感因素。