Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in chinese non-smokers

The influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at ?75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high-density lipoprotein cholesterol (HDLC) and apo AI and lower low-density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy-Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24–0.31] than that reported in Caucasians (0.12; 95% CI 0.09–0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non-smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits. © 1994 Wiley-Liss, Inc.     

Role of genetic variation at the Apo AI-CIII-AIV gene cluster in determining plasma Apo AI levels in boys and girls

We have investigated the effect of the G/A substitution in the promoter region of the apolipoprotein (apo) AI gene (?75 bp) on plasma lipid, lipoprotein and apolipoprotein levels in a sample of 204 children from central Italy. The subjects included 111 boys and 93 girls, aged 8–11 years old. The frequency of the A allele was 0.19 in the total sample, and 0.21 and 0.17 in boys and girls, respectively. Using analysis of variance, we found the G/A substitution was significantly associated with plasma levels of total cholesterol, LDL cholesterol, apo B, and apo AI in boys, accounting for 7.0, 4.2, 5.3, and 4.3% of the sample variance, respectively. Individuals with an A allele had higher mean levels of these lipid traits than individuals homozygous for the G allele. A dietary intervention study had been carried out in a subset of these children, and the effect of the G/A substitution on plasma apo AI levels remained when boys changed to a low fat low cholesterol diet. However, no significant association was observed in girls between any of the lipid traits and the G/A genotypes. We have previously reported in this sample of children that the two polymorphisms detected with restriction enzyme PvuII, with variable sites in the first intron of the apo CIII gene (Pvu II–CIII) and the apo CIII–AIV intergenic region (Pvu II–AIV), were associated with significant differences on plasma apo AI levels. We found that the association reached statistical significance in boys only in this study. Taking these three polymorphisms together, the effects on plasma apo AI levels were additive in boys, accounting for 20.0% of the sample variance. Boys having the genotype GG/V^?V⁺ of the G/A substitution and the PvuII–AIV RFLP had mean apo AI levels 36 mg/dl lower than boys with the genotype GA + AA/V^?V^?. In girls, however, there was evidence of significant interaction of effects between the PvuII–AIV RFLP and the G/A substitution (P < 0.04), with the A allele being associated with higher levels of plasma apo AI only in girls having the rare allele (V⁺) of the PvuII–AIV RFLP. We conclude that genetic variation at the apo AI-CIII-AIV gene cluster is having a major impact on the determination of plasma apo AI levels in this sample of young boys, with additive effects due to functional changes at several places in this gene cluster detected directly (G/A) or in allelic association with the PvuII–CIII and PvuII–AIV polymorphisms. These effects are not modulated by diet but are modulated by other factors, possibly hormones, which are present in girls. © 1993 Wiley-Liss. Inc.     

New MspI polymorphism at +83 bp of the human apolipoprotein al gene: Association with increased circulating high density lipoprotein cholesterol levels

We recently showed that loss of a MspI restriction site in the 5′-end (intron 1) of the apolipoprotein (apo) AI gene is due to a C to T transition (+83 bp) and/or a G to A transition (+84 bp). Since this region may be relevant to the regulation of apo AI gene expression and therefore to plasma high density lipoprotein cholesterol (HDL-C), we explored the association between this MspI polymorphic site and circulating HDL-C levels in 243 healthy Caucasians. There were 143 aged 18–67 years (60 males and 83 females) and 100 aged 6–12 years (58 males and 42 females). We also compared this association with a known MspI polymorphic site, a G to A transition at −75 bp of the apo AI gene. The rare allele (−) frequency for the polymorphism at +83 bp was 4.1% and 22.1% for the polymorphism at −75 bp. Subjects heterozygous for the loss of the MspI restriction site at +83 bp (genotype: M2+−, n = 20) had higher HDL-C levels than M2++ subjects (mean ± SD: 1.73 ± 0.31 vs. 1.41 ± 0.39 mmol/l, P < 0.05 for adults; 1.71 ± 0.33 vs. 1.34 ± 0.29 mmol/l, P < 0.01 for children). Adults with the G to A substitution at −75 bp also had higher HDL-C levels (1.56 ± 0.36 mmol/l for AA, 1.53 ± 0.38 mmol/l for GA, and 1.36 ± 0.38 mmol/l for GG, P < 0.05); this difference was not observed in the children. The MspI polymorphisms at both sites were in linkage disequilibrium. Their joint effect on the HDL-C levels was also significant and individuals with rare alleles (−) at both sites had the highest HDL-C levels. In an analysis of variance, the MspI polymorphism at +83 bp, and at −75 bp and gender independently accounted for 6.5%, 1.7%, and 5.9%, respectively, of the variance in circulating HDL-C levels when age was controlled as a covariate. We conclude that loss of the MspI site by the C to T (+83 bp) and/or the G to A (+84 bp) transitions is highly associated with increased HDL-C levels. The association appears to be more significant than that of the G to A transition at −75 bp. © 1996 Wiley-Liss, Inc.     

Sources of variability of human plasma apolipoprotein A-IV levels and relationships with lipid metabolism

Plasma apolipoprotein (apo) A-IV concentration was determined by immunoelectrophoretic assay (EIA) in 119 nuclear families. No significant effect of concomitants such as age, weight, height, body mass index, tobacco, and alcohol consumption was observed on apo A-IV levels in men and in boys. In women, contraceptive use and hormonal status affected apo A-IV levels. In girls, only age influenced the quantitative phenotype. After adjusting by specific concomitants significant correlations were observed between apo A-IV levels and triglycerides, apolipoprotein A-I and apo B levels, suggesting a role of apolipoprotein A-IV in the hepatic lipid metabolism. Intrafamilial correlations were estimated to investigate the plausibility of a common family factor. The results obtained in this study showed a significant correlation between family members with the exception of mother-daughter pairs. Using a variance components model, the contribution of genetic and environmental factors was then investigated. Different statistical models were used and two major hypotheses were statistically acceptable: the first hypothesis supports that shared and specific environmental factors explain 35 and 65%, respectively, of the total adjusted plasma apo A-IV variation. The fraction of apo A-IV variability attributable to genetic factors was null. The second hypothesis supports that the fraction of variability attributable to apo A-IV genetic variation is 67% and the common spouse environmental factors are responsible for 33% of the total variability and no specific environmental effect was found. Among the two hypotheses, taking account of the metabolism function, we support the first one without excluding gene- environment interactions which could mask the genetic influence. © 1994 Wiley-Liss, Inc.     

脑梗死患者载脂蛋白AI基因多态性分布的病例对照研究

目的 观察载脂蛋白ＡＩ基因多态性在动脉粥样硬化脑梗死患者中的分布,探讨基因型与脑梗死的关系。方法 用聚合酶链反应技术（ＰＣＲ）检测北京地区１９９例脑本钱 ２０４例健康人的载脂蛋白ＡＩ基因启动子和第一内含子两个ＭｓｐＩ酶发位点限制性片段长度多态民生（ＲＬＦＰ）。结果 北京地区４０３例受检者中载脂蛋白ＡＩ基因启动子均以Ｍ１＋＝和Ｍ１＋－为主要基因型,第一内含子大多数为Ｍ２＋＋基因型;脑梗组ＭＡ＋－基因     

Genetic epidemiology of differences in low-density lipoprotein (LDL) cholesterol concentration: possible involvement of variation at the apolipoprotein B gene locus in LDL kinetics

Circulating levels of low-density lipoprotein (LDL) vary considerably within and between populations, paralleled by differing coronary heart disease (CHD) mortality rates. We have previously shown that variation in the apolipoprotein (apo) B gene as associated with certain restriction fragment length polymorphisms (RFLPs) influences the metabolism of LDL in the U.K. population. To investigate a possible genetic contribution to variation in LDL levels in differing populations we have extended this original study. RFLPs of the apo B gene were determined in samples of individuals from the United Kingdom, Finland, Italy, Spain, and Africa. Significant associations of LDL fractional catabolic rate with the apo B EcoRI and XbaI RFLP genotypes were detected only in the two North European populations. In the African population sample, the XbaI RFLP displayed a significant association with LDL apo B synthesis. The data suggest that variation in the apo B gene influences the metabolism of LDL and that it is different in individuals of different ethnic background.     

Association of a polymorphism in the apo AI gene promoter with hyperalphalipoproteinemia

The distribution of a polymorphism due to an Adenine to Guanine transition in the ApoAI gene has been studied in 136 women and 108 men, through amplification of the promoter region of the gene and allele-specific oligonucleotide hybridization. The allelic frequencies for the A allele were 0.10, 0.14 and 0.27 in women and 0.08, 017 and 0.14 in men for the lowest decile, intermediate group and the highest decile of HDL-cholesterol levels, respectively. Statistical analysis showed that the A allele was associated with high HDL-cholesterol levels in women, but not in men.Corresponding author.     

支气管肺发育不良基因表达调控异常研究进展

支气管肺发育不良(BPD)是早产儿最常见的慢性肺部疾病。BPD由多种因素引起,其本质是在遗传易感性的基础上,各种环境因素引起的肺损伤和发育中的未成熟肺修复之间的不平衡。研究显示BPD致病分子机理多涉及炎症细胞因子、非编码RNA和各种信号通路因子的异常表达调控。这些相关基因的异常表达,不仅影响了胚胎或早期胎儿肺的正常发育,并阻碍了新生肺损伤后肺的修复,或导致肺功能不全。单独或协同影响了BPD的发生发展。同时研究发现环境风险因素如高氧暴露、炎症导致基因表达异常也是BPD发生的原因之一,环境和基因共同作用推动了BPD的发生发展。     

IGF-1基因启动子区CA重复序列多态性与代谢综合征关系研究

目的 探讨胰岛素样生长因子1（IGF-1）基因启动子区CA重复序列多态性与代谢综合征（MS）的关系.方法 收集北京市东城区常住人口1047例,采用2005年国际糖尿病联盟标准诊断代谢综合征.将受试者的基因组DNA应用聚合酶链反应扩增,再通过选择不同长度的纯合子样本测序确定CA重复的次数,以确定等位基因.同时测量身高、体重、腰围、血糖、血脂、胰岛素及血IGF-1.结果 （CA）19纯合组MS患病率显著低于不携带（CA）19组（9.1% vs 24.0%,Х^2=18.05,P＜0.01）及（CA）19杂合组（9.1% vs 18.3%,Х^2=8.55,P＜0.01）;三组间血IGF-1水平差异有统计学意义[（114.0±52.6）μg/L vs（136.6±80.5）μg/L vs（129.2±49.1）μg/L,F=3.16,P＜0.05],（CA）19纯合组血IGF-1水平低于不携带（CA）19组及（CA）19杂合组.三组间体重指数（BMI）、腰围（WC）、甘油三酯（TG）、空腹胰岛素（Fins）、2hIns及胰岛素敏感性指数（ISI）差异均有统计学意义（P＜0.05）,（CA）19纯合组的BMI、WC、TG、FIns、2hIns均低于另两组,而ISI高于另两组.结论 IGF-1基因启动子区CA重复序列多态性与汉族人群MS发病有关.     

Genetic and environmental influences on binge eating in the absence of compensatory behaviors: a population-based twin study

OBJECTIVE: The current study explores the extent to which genetic and environmental factors influence liability to binge eating in the absence of compensatory behaviors (BE) in a population-based sample of twins. METHOD: Questionnaire data on 8,045 same-sex and opposite-sex twins, aged 18-31 years, from a Norwegian twin registry were used to assess BE during the last 6 months. RESULTS: The best-fitting biometrical model suggested that the heritability of BE was 41% (95% confidence interval [CI]: 0.31-0.50). Individual environmental factors accounted for the rest of the variance (59%; 95% CI: 0.50-0.69). No significant sex differences were found, but the statistical power to detect such effects was low. Shared environmental influences on the liability to BE in males could not be ruled out. DISCUSSION: The findings indicate significant additive genetic influences on BE, supporting the validity of the core features of binge eating disorder as a diagnostic category.     

The-2548G/A polymorphism in the human leptin gene promoter region is associated with plasma free leptin levels; interaction with adiposity and gender in healthy subjects

A common -2548G/A promoter variant of the human leptin gene has recently been shown to be associated with variations in circulating leptin levels but available data are still conflicting. The aim of this study was to explore potential associations between the -2548G/A polymorphism and adiposity-related variables, plasma total leptin levels, as well as soluble leptin receptor (sOB-R) levels and free leptin in a group of healthy Greek subjects. One hundred eighteen consecutively enrolled subjects [62 females, 56 males; mean age+/-SD: 17.7+/-1.8 years; body mass index (BMI) range: 15.4-35.9 kg/m2] were genotyped for the -2548G/A polymorphism and their BMI, fat free mass, % fat mass, fasting plasma total leptin and sOB-R levels were determined. The ratio leptin/sOB-R was used as an index of free leptin. No significant differences in genotype and allele frequencies of the -2548G/A polymorphism were detected between normal weight and overweight subjects, and no association was found between this polymorphism and BMI, fat mass or plasma total leptin levels. However, the -2548G/A polymorphism was found to be associated with circulating free leptin levels in a gender specific manner. More specifically, compared to carriers of the -2548G allele, female subjects with the A/A genotype had higher age and fat mass adjusted mean (+/-SE) plasma concentrations of sOB-R (32.9+/-7.2 vs. 25.6+/-3.8 ng/ml, P=0.05), and significantly lower (approx. 50%) leptin/sOB-R values (0.74+/-0.25 vs. 1.42+/-0.13, P=0.02). Furthermore, multiple regression analysis revealed that, after adjustment to fat mass, the -2548G/A genotype and gender are significantly associated with free leptin index in the entire study sample. Similar regression models revealed a significant interaction of gender and genotype when considered in addition to fat mass, or fat mass and genotype when considered in addition to gender, as predictors of free leptin index. In conclusion, the common -2548G/A promoter variant of the human leptin gene is associated with plasma free leptin levels through an interaction with adiposity and gender in healthy subjects.     

Factors associated with teenage pregnancy in the European Union countries: a systematic review

BACKGROUND: As part of the REPROSTAT2 project, this systematic review aimed to identify factors associated with teenage pregnancy in 25 European Union countries. METHODS: The search strategy included electronic bibliographic databases (1995 to May 2005), bibliographies of selected articles and requests to all country representatives of the research team for relevant reports and publications. Primary outcome measure was conception. Inclusion criteria were quantitative studies of individual-level factors associated with teenage (13-19 years) pregnancy in EU countries. RESULTS: Of 4444 studies identified and screened, 20 met the inclusion criteria. Most of the included studies took place in UK and Nordic countries. The well-recognized factors of socioeconomic disadvantage, disrupted family structure and low educational level and aspiration appear consistently associated with teenage pregnancy. However, evidence that access to services in itself is a protective factor remains inconsistent. Although further associations with diverse risk-taking behaviours and lifestyle, sexual health knowledge, attitudes and behaviour are reported, the independent effects of these factors too remain unclear. CONCLUSIONS: Included studies varied widely in terms of methods and definitions used. This heterogeneity within the studies leaves two outstanding issues. First, we cannot synthesize or generalize key findings as to how all these factors interact with one another and which factors are the most significant. Second, it is not possible to examine potential variation between countries. Future research ensuring comparability and generalizability of results related to teenage sexual health outcomes will help gain insight into the international variation in observed pregnancy rates and better inform interventions.     

Comparison of the Concordance of Cardiometabolic Diseases and Physical and Laboratory Examination Findings between Monozygotic and Dizygotic Korean Adult Twins: A Cross-Sectional Study Using KoGES HTS Data

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (>20 years) based on the Korean Genome and Epidemiology Study data (2005–2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors.     

学龄儿童载脂蛋白CⅢ基因变异与血脂谱的关系研究

为了解载脂蛋白CⅢ基因多态性与学龄儿童血脂谱变异的关系 ,对 30 8名在校儿童 (7～ 11岁 )进行血脂水平测定及载脂蛋白CⅢ基因SacⅠ位点多态性检测 (PCR RFLP方法 )。结果表明载脂蛋白CⅢ基因SacⅠ位点杂合突变型 (+ - )检出率为 48 7% ,纯合突变型 (+ +)检出率为 7 5 % ,其等位基因 (+)频率为31 8% ,高于上海 (12 % )及白种人 (6 % ) ,与日本人 (34 % )接近 ,提示遗传变异有人群及种族差异 ;不同基因型儿童血脂水平比较显示 ,纯合突变基因型儿童的TG水平高于野生型 (P <0 0 5 ) ;高甘油三酯组 (+ +)基因型频率为 30 0 % ,高于对照组 6 7% (P <0 0 5 ) ;ApoCⅢ SacⅠ位点 (+)等位基因可使TG水平升高0 0 31mmol L。结果提示 ,载脂蛋白CⅢ基因SacⅠ位点突变与儿童甘油三酯血症水平升高相关     

Heritabilities, apolipoprotein E, and effects of inbreeding on plasma lipids in a genetically isolated population: The Erasmus Rucphen Family Study

Despite considerable progress in unravelling the genetic basis of dyslipidemias, most findings are based on families with extreme phenotypes. We studied lipid levels in an extended pedigree ascertained irrespective of phenotype from the population of a recent genetic isolate in the Netherlands. Heritabilities of plasma lipid measures were examined; this analysis also included estimates of the proportion of variance attributable to ApoE genotype. The association between inbreeding and lipids was also considered, as a substantial fraction of the population had known inbreeding. A total of 868 individuals from this pedigree, containing more than 60,000 people over 15 generations, were investigated in this study. Laboratory analysis of these subjects included the determination of fasting plasma lipids. ApoE ɛ2/3/4 status was ascertained using TaqMan assays. Heritabilities for plasma lipids were estimated with adjustments for multiple covariates using SOLAR. Heritabilities for total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), TC/HDL ratio, and TG/HDL ratio were found to be 0.35, 0.56, 0.30, 0.24, 0.49, and 0.39, respectively. The addition of ApoE genotype in the model significantly decreased these estimates (Δh² = −0.030, −0.004, −0.054, and −0.006 for TC, HDL, LDL, and TG). In a further analysis, TC and LDL were positively associated with the extent of inbreeding (p _trend = 0.02 and p _trend = 0.05, respectively). These data provide estimates of lipid heritability unbiased due to selection and suggest that this population represents a good opportunity to localize novel genes influencing plasma lipid levels.     

Race-gender differences in the association of trait anger with subclinical carotid artery atherosclerosis: the Atherosclerosis Risk in Communities Study

This paper examines the association between trait anger and subclinical carotid artery atherosclerosis among 14,098 Black or White men and women, aged 48-67 years, in the Atherosclerosis Risk in Communities Study cohort, 1990-1992. Trait anger was assessed using the 10-item Spielberger Trait Anger Scale. Carotid atherosclerosis was determined by an averaged measure of the wall intimal-medial thickness (IMT) of the carotid bifurcation and of the internal and common carotids, measured by high-resolution B-mode ultrasound. In the full study cohort, trait anger and carotid IMT were significantly and positively associated (p = 0.04). In race-gender stratified analysis, the association was strongest and independent only in Black men, among whom a significant trait anger-carotid IMT relation was observed for both the overall trait anger measure (p = 0.004) and the anger reaction dimension (p = 0.001). In Black men, carotid IMT levels increased across categories of overall trait anger and anger reaction, resulting in clinically significant differences (67 microm (95% confidence interval: 23, 110) and 82 microm (95% confidence interval: 40, 125), respectively) from low to high anger. Sociodemographic, lifestyle, anthropometric, and biologic cardiovascular disease risk factors appear to mediate the relation in Black women, White men, and White women. In conclusion, these findings document disparate race-gender patterns in the association of trait anger with subclinical carotid artery atherosclerosis.     

Understanding the factors associated with differences in caesarean section rates at hospital level: the case of Latin America

As in many other regions of the world, caesarean section (CS) rates in Latin America are increasing. Studies elsewhere have shown that providing feedback to caregivers regarding their own performance relative to their peers can significantly reduce the rates. Our objectives are to calculate risk-adjusted CS rates for hospitals in Latin America and to identify factors associated with differences among risk-adjusted rates. We included 120 randomly selected institutions in eight countries of Latin America, representing 97 095 pregnancies. We used random-effects models to calculate a risk-adjusted rate for each hospital and to identify hospitals significantly higher or lower than a benchmark rate. We conducted a regression analysis to identify characteristics of hospitals associated with differences among risk-adjusted rates.
The overall CS rate was 35%, ranging from 0% to 85%. Risk-adjusted CS rates ranged from 11% to 78%. Three-quarters of hospitals had risk-adjusted rates significantly above the previously identified benchmark of 20%. Characteristics of institutions explained 48% of the variability among risk-adjusted rates, including being a private as opposed to a public institution, having some economic incentive for CS as opposed to no incentive, and having ≥50 maternity beds.
Strategies to halt further increases in CS rates and reduce rates to levels that reflect the best quality of care, are urgently needed worldwide. The involvement of local quality control departments is an essential component in achieving success. Our results can be used to identify institutions that can be targets for further interventions to reduce CS rates.     

2018年中国心血管疾病死亡地点影响因素分析

目的:掌握2018年全国及分省心血管疾病（CVD）死亡地点分布特征,探索人口统计学特征、个人社会经济状况、疾病相关因素、区域社会经济因素等与CVD患者死亡地点之间的关联。方法:利用全国人口死亡信息登记管理系统死因监测数据,采用多水平logistic回归模型探索解释变量与CVD医疗卫生机构死亡的关系。结果:2018年,我...