Plasma apoAV levels are markedly elevated in severe hypertriglyceridemia and positively correlated with the APOA5 S19W polymorphism

OBJECTIVE: The recently discovered apoAV is hypothesized to affect triglyceride metabolism by stimulating the lipolysis of triglycerides in VLDL and chylomicrons. We set out to determine the association between increased serum TG levels, plasma apoAV levels, and polymorphism of the APOA5 gene, with specific emphasis on the APOA5 S19W variation. This mutation alters the endoplasmic reticulum signal peptide and is hypothesized to impair apoAV secretion into the circulation. METHODS AND RESULTS: Two haplotype-tagging APOA5 polymorphisms, APOA5 S19W and APOA5 -1131T>C and plasma apoAV levels were determined in a population of patients with severe hypertriglyceridemia (HTG). As compared to a random control population, the allele frequencies of the APOA5 S19W and -1131T>C rare variants were significantly increased in HTG patients. Furthermore, the HTG population exhibited markedly elevated plasma apoAV levels that were positively correlated with serum TG levels. Plasma apoAV levels were positively correlated with occurrence of the APOA5 S19W rare variant. CONCLUSIONS: The increased allele frequencies of the APOA5 S19W and -1131T>C rare variants in the HTG population are in agreement with previous reports. Our data show a positive correlation between apoAV and TG levels. Moreover the finding of a positive association between apoAV levels and the APOA5 S19W rare variant is in disagreement with the hypothesis that this variant is poorly secreted.     

Impact of APOA5/A4/C3 genetic polymorphisms on lipid variables and cardiovascular disease risk in French men

OBJECTIVE: The goal of the present study was to assess the impact of 4 single nucleotide polymorphisms (SNPs) of APOA5/A4/C3 gene cluster on lipid levels and coronary heart disease (CHD) risk in French men. METHODS: A total of 442 men with CHD were recruited from the university hospital and compared to 475 men free of CHD from the population of the same geographical area. The APOA5 S19W, APOA5 -l2,238T>C, APOA4 T347S and APOC3 -482C>T SNPs were examined. RESULTS: The APOA5 S19W polymorphism was associated with plasma triglyceride levels. In multivariate logistic regression analyses the odds ratio (OR [95% Cl]) of hypertriglyceridemia (3rd vs. 1st tertile of triglyceride distribution) was 3.60 [1.38-9.42] in control subjects bearing at least one APOA5 19W variant. Haplotype analyses revealed a significant association between the 2111 haplotype and high triglyceride levels (+1.94 +/- 0.63 vs. 0.74 +/- 0.36 mmol/l for the 1111 haplotype p < 0.002). There was, in contrast, no significant difference in SNP distribution between CHD patients and controls. The age-adjusted OR of CHD were 1.46 [0.96-2.23], 0.79 [0.60-1.05], 0.91 [0.69-1.21] and 0.91 [0.69-l.22] in carriers of the APOA5 19W, APOA5 -12,238C, APOA4 347S and APOC3 -482T variants, respectively. There was also no significant difference in APOA5/A4/C3 haplotype distribution in patients and controls. CONCLUSION: The APOA5 19W variant is associated with increased plasma triglycerides. However, there is no evidence that APOA5 S19W, -12,238T > C, APOA4 T347S and APCC3 -482C > T SNPs are major risk factors of CHD in French men.     

Genetic variations of apolipoprotein A5 gene is associated with the risk of coronary artery disease among Chinese in Taiwan

Recently, a T/C polymorphism of the promoter region of the APOA5 gene at position -1131 and a G/T polymorphism at position 553 were found to be associated with increased levels of plasma triglyceride. Triglyceride plays a role in coronary artery disease (CAD), so this case-control study tested for a possible link between these two APOA5 polymorphisms, their common haplotypes and the risk of CAD. The subjects included 211 CAD patients and 677 unrelated controls. A significantly higher level of triglycerides and a lower level of high-density lipoprotein cholesterol (HDL-C) were noted for carriers with -1131C than for non-carriers (P<0.001 and 0.013, respectively) among controls. Plasma triglyceride levels were significantly higher (P=0.014) in controls with genotypes that contained the c.553T allele than in homozygotes for the G allele. Subjects homozygous for the wild-type haplotype had significantly lower triglyceride levels and higher HDL-C levels than subjects with all other haplotype pairs. The -1131C homozygous carriers and c.553T heterozygous carriers were found more frequently in 211 patients with CAD than in the 317 age/sex-matched controls (P=0.008 and 0.023, respectively) in univariate analysis. The significant association between c.553T allele carriers with CAD remained in multivariate regression analysis (OR, 1.79; CI, 1.07-3.00; P=0.028), after adjustments were made for other risk factors. Notably, haplotype analysis further verified that the APOA5 -1131C and c.553T bi-loci haplotype was significantly overpresented in CAD, as compared to the controls. These results indicate that the variants of APOA5 gene modulate plasma triglyceride and may use them to predict CAD susceptibility in Taiwanese Chinese.     

Contribution of APOA5−1131C allele to the increased susceptibility of diabetes mellitus in association with higher triglyceride in Korean women

Apolipoprotein A5 (APOA5) −1131C allele is associated with higher triglyceride, an independent cardiovascular risk factor and a commonly recognized lipid abnormality in diabetes mellitus (DM). We investigated the association of APOA5 −1131T>C or S19W with DM. Study subjects were all women and categorized into metabolically healthy controls (n = 2033) and DM subjects (n = 304). Association of APOA5 −1131T>C with DM was calculated by odds ratio (OR). Anthropometric parameters, fasting glucose, and lipid profiles were measured. C carriers, particularly those with CC homozygote, had higher triglyceride and lower high-density lipoprotein cholesterol in both healthy controls (P < .001 and P < .001) and DM patients (P = .002 and P = .006) after the adjustment for age, body mass index, menopause, smoking, and drinking. APOA5 −1131C allele was associated with an increased risk of DM (OR, 1.61 [95% confidence interval {CI}, 1.23-2.10]; P < .001) after adjustment for the above confounders. Further adjustment for fasting triglyceride or/and high-density lipoprotein cholesterol attenuated a little bit, but still significantly increased the risk of DM in C carriers (OR₂, 1.36 [95% CI, 1.02-1.80]; P = .035 and OR₃, 1.36 [95% CI, 1.032-1.79]; P = .029, respectively). Interestingly, C allele carriers in DM patients showed a positive correlation between fasting glucose and triglyceride after the adjustment (r = 0.172, P = .035). On the other hand, this significant correlation was not observed in healthy women. Regarding S19W, minor allele was not found in our study population from prescreening test. In conclusion, APOA5 −1131C allele may contribute to the increased susceptibility of DM in Korean women. In addition, positive correlation between fasting glucose and triglyceride in C carriers of DM patients suggested that C allele in hyperglycemic states may be more susceptible to the risk of cardiovascular disease.     

The -1131 T>C and S19W APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease: an angiographic study

High plasma concentrations of triglycerides (TG) and apolipoprotein C-III (ApoC-III) are well-known risk factors for cardiovascular disease. Two variants of the recently discovered APOA5, 1131 C>T and S19W, have been associated with hypertriglyceridemia, whereas their relation with coronary artery disease (CAD) remains controversial. Nine hundred and thirteen angiografically defined patients (669 CAD and 244 CAD-free) were genotyped for APOA5 -1131 C>T and S19W polymorphisms. Carriership of the APOA5 -1131 C allele was identified, by multiple linear regression models, as a significant independent predictor for both TG (standardized beta-coefficient=0.112; p=0.010) and ApoC-III variability (standardized beta-coefficient=0.113; p=0.013). Similarly, APOA5 19W allele carriership was a significant independent predictor for both TG (standardized beta-coefficient=0.113; p=0.007) and ApoC-III variability (standardized beta-coefficient=0.088; p=0.045). Despite the association with at-risk lipid profile, no significant difference was detected in the distribution of both APOA5 gene polymorphisms between subjects with or without CAD. Moreover, homozygous carriers of the APOC3 -455 C, another TG- and ApoC-III raising variant, showed a significant increased risk for CAD (OR 1.90 with 95% CI 1.002-3.62; p=0.049; by multiple logistic regression). Different genotypes, i.e., APOA5 and APOC3 variants, may lead to similar biochemical phenotypes, namely hypertriglyceridemia, but to contrasting clinical phenotypes such as the presence of angiographically proven CAD.     

中国人内源性高甘油三酯血症与载脂蛋白A5基因-1131T>C多态性、S19W多态性的相关性

目的探讨中国人内源性高甘油三酯血症患者载脂蛋白A5基因的-1131T〉C多态性及S19W多态性与血脂水平的关系。方法用聚合酶链反应-限制性片断长度多态性分析，对182名内源性高甘油三酯血症患者和200名血脂正常者的载脂蛋白A5基因启动子上游-1131T〉C单核苷酸多态性、编码区的S19W（c．56C〉G）多态性、空腹血脂及载脂蛋白水平进行分析。结果患者的体质指数、血清总甘油三酯和总胆固醇水平较对照组显著升高，高密度脂蛋白胆固醇水平则显著降低。-1131T／C单核苷酸多态性位点T和C等位基因频率在病例组和对照组分别为52．7％、47．3％和67.0％、33．0％。等位基因频率和基因型频率分布符合Hardy-Weinberg平衡定律。T/C基因多态性等位基因T和C频率在两组问的差异有显著性（P〈0．05）；S19W多态性与内源性高甘油三酯血症发病风险未见明显相关性。结论载脂蛋白A5基因-1131C等位基因与血清甘油三酯的升高相关。     

动脉硬化性脑梗死患者载脂蛋白A5基因多态性研究

目的研究载脂蛋白A5基因-1131T>C多态性位点各基因型及等位基因分布频率及其与动脉硬化性脑梗死(arteriosclerotic cerebral infarction,ACI)的关系。方法选择221例湖北地区汉族人群(对照组)及90例ACI患者(ACI组),应用聚合酶链反应限制性片段长度多态性对每个个体的基因型进行鉴定。同时,采用酶法和免疫比浊法对研究对象血脂进行检测。结果2组间除性别、年龄、体重指数无显著差异外,其他各项指标(吸烟、收缩压、舒张压、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1及载脂蛋白B)均有显著差异(P<0.05);ACI组稀有等位基因C携带者甘油三酯水平明显高于C非携带者,2组中TT、TC、CC 3种基因型甘油三酯水平差异有显著性意义(P<0.05);ACI组稀有等位基因C的频率明显高于对照组(χ2=5.568,P=0.018)。结论apoA5-1131C等位基因与ACI患者甘油三酯水平升高有关,其不同基因型及等位基因在湖北汉族人群及ACI患者中的分布不同,可能与该地区人群ACI危险性有关。     

汉族人载脂蛋白A5基因-1131T＞C多态性与2型糖尿病合并冠心病的相关性研究

目的 探讨我国北方地区汉族人载脂蛋白A5基因（APOA5）-1131T＞C多态性对血脂的影响及其与2型糖尿病合并冠心病的关系.方法 应用聚合酶链反应限制性片段长度多态性（PCR-RFLP）技术检测了136例健康对照者、163例2型糖尿病患者（DM组）和114例经冠状动脉造影确诊的2型糖尿病合并冠心病患者（DM＋CHD组）APOA5-1131T＞C多态性基因型和等位基因频率分布,同时检测了研究对象的血脂、脂蛋白和载脂蛋白水平.结果 健康对照组APOA5-1131T＞C多态性与血清甘油三酯（TG）水平密切相关,C等位基因携带者TG水平明显高于TT基因型（1.38比0.91 mmol/L,P＜0.001）.2型糖尿病合并冠心病组APOA5-1131C等位基因频率明显高于对照组（38.4%比28.3%,P=0.023）,TT、TC、CC基因型频率在DM＋CHD组和对照组分别为33.9%、55.4%、10.7%和50.4%、42.5%、7.1%,两组间差异具有统计学意义（P＜0.05）.而2型糖尿病组和对照组相比,APOA5-1131T＞C多态性基因型频率和等位基因频率分布均无差异.结论 APOA5-1131T＞C多态性对人群TG水平有极显著影响,C等位基因与2型糖尿病合并冠心病的患病风险有一定关系.     

The apolipoprotein A-V genotype and plasma apolipoprotein A-V and triglyceride levels: prospective risk of type 2 diabetes. Results from the Northwick Park Heart Study II

Aims/hypothesis We sought to establish the relationship between plasma apolipoprotein A-V (APOA5, previously known as apoA-V) and triglyceride levels and to determine the impact of the APOA5 genotype on APOA5 levels and development of type 2 diabetes in a 15-year follow-up study of healthy UK men. Materials and methods APOA5 −1131T>C and S19W genotypes were determined in 2,490 men, of whom 145 subsequently developed type 2 diabetes. In a subset of 299 men, we also determined APOA5 levels. Results Plasma APOA5 levels positively correlated with triglycerides (r=0.18, p<0.002) and were not different in men who subsequently developed type 2 diabetes compared with healthy men (p=0.7). Carriers of either APOA5 W19 or −1131C had, as expected, higher plasma triglycerides. However, while W19 carriers had significantly higher APOA5 levels (p=0.0003), APOA5 levels were not associated with −1131T>C (p=0.63), reinforcing the idea that the reported −1131C association with triglycerides levels is due to linkage disequilibrium with variants in the APOC3 gene, and not due to the direct effect on APOA5 levels. Overall no effect of APOA5 −1131T>C or S19W was found on type 2 diabetes risk. Conclusions/interpretation In contrast to animal studies, in man, plasma APOA5 positively correlates with plasma triglyceride levels. In prospective analysis, with the caveat that numbers were small, APOA5 genotypes do not appear to have an impact on risk of development of type 2 diabetes.     

The -1131T>C polymorphism in the apolipoprotein A5 gene is related to hypertriglyceridemia in Taiwanese aborigines

The prevalence of hypertriglyceridemia, considered to be an independent risk factor for the development of cardiovascular disease, is high in Taiwanese aborigines. This study was undertaken to examine the effect of the -1131T>C polymorphism in the apolipoprotein A5 gene on serum triglyceride levels in female Taiwanese aborigines. This was a cross-sectional study, and a total of 316 unrelated female Taiwanese aborigines were genotyped at the -1131T>C polymorphism in apolipoprotein A5 using the polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride > or = 150 mg/dL was defined as the hypertriglyceridemia group and triglyceride < 150 mg/dL was considered to be the control group. The frequency of the minor C allele was significantly higher in the hypertriglyceridemia group (0.53) than in the control group (0.35) (p < 0.001). The frequency of this rare allele was comparable to that in Japanese and Han Chinese, but was higher than that in Caucasians. In a multiple logistic model adjusted for possible confounders, C allele-containing variants were independently associated with greater risks (CT genotype: OR = 3.28, 95% CI = 1.43-7.56; CC genotype: OR = 5.86, 95% CI = 2.15-15.99) of hypertriglyceridemia than the TT genotype (p < 0.01), notably with the CC homozygote exhibiting the greatest risks. The genotype polymorphisms were also associated with serum triglyceride concentrations in a linear fashion (for trend, p < 0.05). Our results indicate that the -1131T>C polymorphism of the Apo A5 gene influences serum triglyceride levels in female Taiwanese aborigines, and that differences exist in the frequency of the C allele among people of various ethnicities.     

冠心病患者载脂蛋白A5基因多态性与冠状动脉病变程度的相关性

目的分析冠心病患者载脂蛋白A5基因多态性与冠状动脉病变程度的关系。方法采用聚合酶链反应—限制片长多态性技术分别对260例经冠状动脉造影确诊为冠心病的研究对象载脂蛋白A5基因-1131T>C和c.553G>T多态性位点基因型进行检测;其冠状动脉病变程度由病变支数及Gensini积分表示。结果冠心病患者载脂蛋白A5-1131CC基因型人群和c.553T等位基因携带者血清甘油三酯水平明显高于-1131T等位基因携带者和c.553GG基因型人群(P=0.016和0.008);不同冠状动脉病变支数组间载脂蛋白A5基因型分布和不同基因型间Gensini积分的差异无统计学意义(P>0.05);冠状动脉病变支数和Gensini积分与糖尿病发病率呈显著正相关(r=0.141和0.143,P均<0.05),而与血清高密度脂蛋白胆固醇水平则呈显著负相关(r=-0.129和-0.164,P均<0.05)。结论冠心病患者载脂蛋白A5基因-1131T>C和c.553G>T多态性与其血清甘油三酯水平存在一定的相关性,但与冠状动脉病变程度无关。     

Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population

BACKGROUND: Apolipoprotein A5 (APOA5) plays an important role in plasma triacylglycerol (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, and c.1259T>C) in the APOA5 gene define three common haplotypes (APOA5*1, APOA5*2, and APOA5*3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males. DESIGN AND METHODS: Eighty-eight APO E3/3 volunteers [67 with (-1131T and 56C) APOA5*1 haplotype, 12 with (-1131C and 56C) APOA5*2 haplotype, and nine with (-1131T and 56G) APOA5*3 haplotype] underwent a fat load test consisting of the consumption of 1 g of fat per kilogram body weight and 60,000 IU vitamin A. Blood samples were taken at time 0, at every hour until the sixth hour, and at every 2.5 h until the 11th hour. Total plasma cholesterol (C) and TG, and C, TG, apolipoprotein B-100, apolipoprotein B-48, and retinyl palmitate in lipoprotein fractions were determined. RESULTS: Subjects with the APOA5*2 and APOA5*3 haplotypes had a higher area under the curve of total plasma TG (P = 0.03), large TG-rich lipoprotein (TRL)-TG (P = 0.02), small TRL-TG (P = 0.04), small TRL-C (P = 0.04), large TRL-C (P = 0.03), and small apolipoprotein B100 (P = 0.04) than subjects with the APOA5*1 haplotype. CONCLUSIONS: Our findings show that the presence of the APOA5*2 and APOA5*3 haplotypes in the APOA5 gene is associated with a higher postprandial response that could be involved in the higher risk of coronary heart disease associated with the 56G and -1131C alleles.     

Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study

Polymorphisms in the APOC3 and APOA5 genes, from the APOA1/APOC3/APOA4/APOA5 gene cluster on chromosome 11q23, have been associated with interindividual variation in plasma triglycerides. APOA5 polymorphisms implicated include 2 in the promoter region (-1131 T/C and -3 A/G) and 1 in exon 2 (+56 C/G). APOC3 polymorphisms implicated include 1 (SstI) in the 3' untranslated region and 1 (-2854 G/T) in the APOC3-APOA4 intergenic region. We analyzed the associations of haplotypes and multilocus genotypes of these polymorphisms on longitudinal serum triglyceride profiles in 360 African American and 823 white subjects from the Bogalusa Heart Study. Subjects were examined from 2 to 8 times (mean +/- SD, 5.4 +/- 1.3) between 1973 and 1996, at ages ranging from 4 to 38 years, with 1978 observations in African Americans and 4465 in whites. Serum triglycerides were significantly higher among whites across all ages. Allele frequencies differed significantly between African Americans and whites at all but the APOA5 +56 C/G locus. Linkage disequilibrium among the loci was higher in whites and haplotype diversity lower: 6 haplotypes had estimated frequencies of more than 1% in African Americans, 5 in whites. Individually, all polymorphisms except APOC3 -2854 G/T showed significant associations with triglyceride levels in the full sample. However, genotype models including all 5 loci showed significant triglyceride associations for only 3 (APOC3 SstI, APOA5 -1131 T/C, and APOA5 +56 C/G); significant interactions among them indicated their effects were not independent. Neither APOC3 -2854 G/T nor APOA5 -3 A/G had significant effects when the other 3 loci were in the models. The EM algorithm was used to estimate haplotype frequencies and assign haplotype probabilities to individuals, which is conditional on their genotypes; individuals' haplotype probability vectors were then used as predictors in multilevel mixed models of longitudinal triglyceride profiles. Of haplotypes comprising, in order, APOC3 SstI and -2854 G/T and APOA5 -1131 T/C, -3 A/G, and +56 C/G, 3 were significantly associated with higher triglycerides, even after adjusting for multiple tests: GGTAG (P = .002), GTTAG (P < .0001), and CGCGC (P = .0002). Each GGTAG haplotype carried would be expected to raise triglyceride levels (relative to those of GTTAC homozygotes) by approximately 19 mg/dL, each GTTAG haplotype by approximately 15 mg/dL, and each CGCGC haplotype by approximately 7 mg/dL. Haplotypes comprising the 3 loci implicated by genotype analyses (SstI, -1131 T/C, and +56 C/G) were also tested: haplotypes C_C_C and G_T_G significantly raised triglycerides, even after adjustment for multiple comparisons (P < .002 for both), with each copy of C_C_C expected to raise triglycerides by approximately 7 mg/dL and each copy of G_T_G by approximately 15 mg/dL. Overall, our findings support those of others in associating specific polymorphisms and haplotypes in the APOA1/C3/A4/A5 gene cluster with higher serum triglyceride levels. However, the degree to which polymorphisms in the APOC3 and APOA5 genes may be independently associated with triglyceride levels remains to be determined.     

Apolipoprotein A5 gene IVS3+G476A allelic variant confers susceptibility for development of ischemic stroke

BACKGROUND: T-1131C, T1259C and IVS3+G476A are naturally occurring variants of the apolipoprotein A5 (APOA5) gene and their possible impact on the development of ischemic stroke was investigated in the present study. METHODS AND RESULTS: PCR-RFLP assays were used to determine the distributions of the APOA5 alleles in small-vessel, large-vessel and mixed subgroups of 378 patients and in 131 stroke-free control subjects. Increased triglyceride levels were found in subjects carrying -1131C, 1259C, IVS3+476A alleles in all stroke groups and in the controls. The -1131C and IVS3+476A alleles, but not the T1259C variant, showed significant accumulation in all stroke subgroups. Logistic regression analysis adjusted for age, gender, body mass index, total cholesterol level, ischemic heart disease, hypertension, diabetes mellitus, smoking-and drinking habits revealed that the IVS3+476A allele represents independent susceptibility factor for stroke (odds ratio for small-vessel: 4.748; large-vessel: 3.905; mixed: 2.926; overall: 3.644 at 95% confidence interval; p<0.05), we could also confirm the previously verified pathogenic role of the -1131C variant. CONCLUSIONS: All of the 3 APOA5 variants are associated with elevated triglycerides, but only the -1131C and the IVS3+476A alleles confer risk for all types of ischemic stroke; such an association could not be detected for the 1259C allele.     

冠心病痰证与载脂蛋白A5 c.553G>T基因多态性的关系研究

目的探讨载脂蛋白A5(APOA5)c.553G>T基因多态性与冠心病痰证的关系。方法运用聚合酶链反应-限制性片段长度多态性分析技术(PCR-RFLP)对湖南地区58例冠心病痰证、51例冠心病非痰证、73例非冠心病痰证患者及74名健康人的APOA5c.553G>T基因型进行检测,同时检测所有研究对象的血脂、血压及体质量指数。结果 256例受检者中,APOA5c.553G>T位点GG型221例(86.33%),GT型35例(13.67%),TT型0;G等位基因频率93.16%,T等位基因频率6.84%。c.553GT型血清TG水平明显高于GG型。病例-对照研究提示c.553T等位基因是冠心病痰证发生的危险因素,但多因素Logistic回归分析不支持c.553T是上述病证发生的独立危险因素。结论 APOA5c.553G>T基因多态性不是冠心病痰证的独立危险因素,c.553GT基因型可能与血清三酰甘油水平升高有关。     

冠心病患者载脂蛋白A5和载脂蛋白C3基因多态性的研究

目的研究中国北方汉族人群中载脂蛋白A5基因(APOA5)-1131F／C、56C／G多态性和载脂蛋白C3基因(APOC3)-482C／T多态性与冠心病的关系。方法采用聚合酶链反应．限制性片段长度多态性(PCR-RFLP)结合聚丙烯酰胺凝胶电泳(PAGE)技术检测了312例经冠状动脉造影确诊的冠心病患和317例健康对照APOA5-1131T／C、56C／G和APOC3-482C／T多态性基因型和等位基因的分布,同时采用生化方法检测了研究对象的血脂水平。结果冠心病组APOA5-1131C等位基因频率明显高于对照组(39．9％比33．3％,P=0．02)。CC纯合子患冠心病的风险是TT纯合子的1.93倍(95％CI：1．12～3．32),且通过Logistie回归分析发现该相关性独立于性别、年龄、体重指数、吸烟史、高血压糖尿病患病史及血清TC、HDK-C、IDL-C水平;冠心病组CC纯合子的TG水平明显高于TC杂合子,而TT纯合子TG水平最低。虽然APOA5-1131T／C和APOC3—482C／T多态性存在连锁不平衡,但前的作用与后无关。结论APOA5-1131T／C基因多态性对人群血清TG水平有影响,APOA5-1131C等位基因可能与我国北方汉族人冠心病的发生相关联。     

载脂蛋白A5-1131T>C(rs662799)多态性与中国汉族非心源性缺血性脑卒中的关联研究

目的探讨中国汉族人群中载脂蛋白A5(APOA5)-1131T>C(rs662799)多态性与缺血性脑卒中的关系。方法选择1119例缺血性脑卒中患者和1027例健康居民作为对照,采用Taqman-MGB探针对载脂蛋白A5-1131T>C位点基因多态性进行检测,并通过文献检索,对符合标准的文献进行荟萃分析,全面探讨中国人群中载脂蛋白A5-1131T>C多态性与缺血性脑卒中的关系。结果研究表明载脂蛋白A5-1131T>C单核苷酸多态性不同等位基因频率和基因型在缺血性脑卒中组和正常对照组分布未见显著统计学差异。校正传统危险因素logistic回归分析显示在隐性模型下,APOA5-1131T>C与血栓性脑卒中相关(p=0.036),荟萃分析结果表明APOA5-1131C等位基因与中国汉族人群脑卒中发生的危险性无相关关系(OR=1.18,95%CI=0.90-1.54)。结论在中国人群中,APOA5-1131T>C多态性与缺血性脑卒中无相关性。     

Association of apolipoprotein A5 gene promoter region -1131T>C with risk of stroke in Han Chinese

Background

Ischemic stroke is a suddenly developing temporary or often permanent damage of the brain. Several candidate genes have been shown to have an impact in the pathogenesis of ischemic stroke. Recently, the − 1131 T > C polymorphism in apolipoprotein A5 (APOA5) gene has been reported to be associated with ischemic stroke in different racial groups, but no data is available currently in Han Chinese. Our study is to investigate the association between the APOA5 gene polymorphism − 1131 T > C and the susceptibility to ischemic stroke in Han Chinese.

Methods

310 controls and 342 patients with classified ischemic stroke were performed to detect the − 1131 T > C alleles genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in independent case-control study.

Results

TG levels of subjects carrying − 1131C allele were elevated compared to the subjects with − 1131 T allele in all ischemic stroke subgroups and in controls. The serum TC, LDL-C and HDL-C levels did not differ between subjects with T or C alleles in each group. The overall distribution of APOA5 − 1131 T > C genotype among stroke patients and controls was significantly different (P < 0.01). Frequencies of CC homozygote and C allele were significantly higher in all stroke subgroups than those in control group. After adjustment for conventional risk factors, logistic regression analysis showed that C allele carrier (CC + CT) of − 1131 T > C was an independent risk factor for all stroke subgroups (P < 0.05).

Conclusions

APOA5 gene − 1131 T > C polymorphism is independently associated with the development of ischemic stroke in Chinese Han population, and CC homozygote may have a promoting effect on ischemic stroke.     

Apolipoprotein A5 gene polymorphisms are associated with non-alcoholic fatty liver disease

Background: Several studies have reported that apolipoprotein A5(APOA5) is involved in the development of non-alcoholic fatty liver disease(NAFLD). However, no research has been performed regarding the association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore the association between APOA5 gene polymorphisms and NAFLD in a Chinese Han population.Methods: Genotypes of the SNPs(rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 in 232 NAFLD patients and 188 healthy controls were determined using polymerase chain reaction(PCR)analysis. Clinical characteristics were measured using biochemical methods.Results: The five single nucleotide polymorphisms(SNPs)(rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 showed no significant association with NAFLD(P 0.05). The rs10750097 with G allele showed a higher serum level of alkaline phosphatase(ALP) compared with C allele in overall series and NAFLD patients(P 0.05). The rs1263173(A/A) carriers showed a higher level of glucose compared to the non-carriers in overall series(P 0.05). The rs17120035(T/T) carriers showed a lower plasma TG level in overall series and NAFLD patients(P 0.05), and the rs662799(G/G) carriers showed higher levels of plasma triglyceride(TG), ALP, and lower level of high-density lipoprotein(HDL) compared to non-carriers in NAFLD patients(P 0.05). No significant difference were observed on the clinic parameters of APOA5 rs3135507(T/T) carriers in both group of overall series and NAFLD patients(P 0.05).Conclusions: The five SNPs(rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 gene are not associated with the risk of NAFLD in the Chinese Han population. The genotypes of rs10750097(G/G), rs1263173(A/A), rs17120035(T/T), and rs662799(G/G) performed a significant effect on clinic characteristics in overall series and NAFLD patients, indicating that these polymorphisms may be associated with NAFLD.     

Prediction of genetic risk for metabolic syndrome

OBJECTIVES: The aim of the study was to identify gene polymorphisms that confer susceptibility to metabolic syndrome in order to allow reliable assessment of genetic risk for this condition. METHODS AND RESULTS: The study population comprised 1788 unrelated Japanese individuals (1033 men, 755 women), including 1017 subjects with metabolic syndrome (634 men, 383 women) and 771 controls (399 men, 372 women). The genotypes for 158 polymorphisms of 133 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of smoking revealed that the -1131T-->C polymorphism of the apolipoprotein A-V gene (APOA5) was significantly associated with the prevalence of metabolic syndrome, with the C allele representing a risk factor for this condition. A stepwise forward selection procedure demonstrated that APOA5 genotype (CC+TC versus TT) significantly affected the prevalence of metabolic syndrome. The C allele of this polymorphism was associated with an increased serum concentration of triglycerides and a decreased concentration of HDL-cholesterol. CONCLUSIONS: Genotype for APOA5 may prove reliable for assessment of genetic risk for metabolic syndrome.