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Apolipoprotein A5 gene variants and the risk of coronary heart disease: a case?control study and meta?analysis.

ABSTRACT: Previous studies have shown that apolipoprotein A5 (APOA5) gene variants are genetic determinants of the concentration of triglycerides, which are a known risk factor for coronary heart disease (CHD). Using the standardized coronary angiography method, 290 CHD patients and 198 non?CHD controls were recruited from Ningbo Lihuili Hospital. In addition, 331 unrelated healthy volunteers were recruited as healthy controls from Ningbo Ximen Community residents. Three variants of the APOA5 gene, S19W, ?1131T>C and 553G>T, were analyzed for their association with CHD. Under a dominant inheritance model, ?1131CT>C was shown to be a CHD risk factor (P=0.030; OR, 1.422; 95% CI, 1.036?1.952). The single nucleotide polymorphism, 553G>T, was found to correlate with the severity of CHD in males (P=0.032). Meta?analysis showed that ?1131T>C was significantly associated with CHD (P<0.0001). By contrast, negative correlations with CHD were observed for S19W and 553G>T. In the present case?control study, APOA5 gene variants were not found to correlate with the risk of CHD in the populations studied; however, ?1131CT>C was shown to be a CHD risk factor under a dominant inheritance model. Meta?analysis showed a significant contribution of ?1131T>C to the risk of CHD, implying an ethnic difference in APOA5 gene variants.

SUBMITTER: Zhou J

PROVIDER: S-EPMC3981035 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Apolipoprotein A5 gene variants and the risk of coronary heart disease: a case‑control study and meta‑analysis.

Zhou Jianqing J Xu Limin L Huang Rong Stephanie RS Huang Yi Y Le Yanping Y Jiang Danjie D Yang Xi X Xu Weifeng W Huang Xiaoyan X Dong Changzheng C Ye Meng M Lian Jiangfang J Duan Shiwei S

Molecular medicine reports 20130816 4

Previous studies have shown that apolipoprotein A5 (APOA5) gene variants are genetic determinants of the concentration of triglycerides, which are a known risk factor for coronary heart disease (CHD). Using the standardized coronary angiography method, 290 CHD patients and 198 non‑CHD controls were recruited from Ningbo Lihuili Hospital. In addition, 331 unrelated healthy volunteers were recruited as healthy controls from Ningbo Ximen Community residents. Three variants of the APOA5 gene, S19W, ...[more]

PMID: 23970179

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Project description:BackgroundTriglycerides (TGs) are proatherogenic lipoproteins involving the risk of coronary heart disease (CHD), while apolipoprotein A5 (APOA5) and apolipoprotein C3 (APOC3) are main lipoproteins composing TG-rich lipoproteins. In this study, we aim to explore the correlation of CHD with APOA5 -1131 T > C and APOC3 -455 T > C single nucleotide polymorphisms (SNPs).MethodsA sum of 210 CHD patients, hospitalized between Jan. 2013 and Mar. 2015 at China-Japan Union Hospital, Jilin University, were selected as our case group and 223 healthy individuals who had physical examination at same hospital at the same period were selected as control group. The frequency distribution of genotypes of APOA5 -1131 T > C and APOC3 -455 T > C SNPs were measured by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Stata 12.0 software was utilized for statistical analyses.ResultsThere was no significant difference on age and sex between case and control group (P > 0.05). History of smoking, drinking, hypertension and diabetes mellitus, body mass index and levels of TG and fasting blood sugar in case group were shown to be higher than control group (P < 0.05), while levels of total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in case group were lower than control group (P < 0.05). Both CC and TC' + CC frequencies of APOA5 -1131 T > C and APOC3 -455 T > C in case group were higher compared to control group (both P < 0.05). Additionally, T allele frequencies of the two SNPs in case group were lower than control group, while C allele in case group has higher frequencies compared to control group (both P < 0.05). The results of meta-analysis under allele and dominant models showed that APOA5 -1131 T > C and APOC3 -455 T > C SNPs are likely to increase the risk of CHD (both P < 0.05).ConclusionAPOA5 -1131 T > C and APOC3 -455 T > C SNPs may play potent roles in the development and progression of CHD.

Project description:Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility.

Project description:Comparison of patients with coronary heart disease and controls in genome-wide association studies has revealed several single nucleotide polymorphisms (SNPs) associated with coronary heart disease. We aimed to establish the external validity of these findings and to obtain more precise risk estimates using a prospective cohort design.We tested 13 recently discovered SNPs for association with coronary heart disease in a case-control design including participants differing from those in the discovery samples (3829 participants with prevalent coronary heart disease and 48,897 controls free of the disease) and a prospective cohort design including 30,725 participants free of cardiovascular disease from Finland and Sweden. We modelled the 13 SNPs as a multilocus genetic risk score and used Cox proportional hazards models to estimate the association of genetic risk score with incident coronary heart disease. For case-control analyses we analysed associations between individual SNPs and quintiles of genetic risk score using logistic regression.In prospective cohort analyses, 1264 participants had a first coronary heart disease event during a median 10·7 years' follow-up (IQR 6·7-13·6). Genetic risk score was associated with a first coronary heart disease event. When compared with the bottom quintile of genetic risk score, participants in the top quintile were at 1·66-times increased risk of coronary heart disease in a model adjusting for traditional risk factors (95% CI 1·35-2·04, p value for linear trend=7·3×10(-10)). Adjustment for family history did not change these estimates. Genetic risk score did not improve C index over traditional risk factors and family history (p=0·19), nor did it have a significant effect on net reclassification improvement (2·2%, p=0·18); however, it did have a small effect on integrated discrimination index (0·004, p=0·0006). Results of the case-control analyses were similar to those of the prospective cohort analyses.Using a genetic risk score based on 13 SNPs associated with coronary heart disease, we can identify the 20% of individuals of European ancestry who are at roughly 70% increased risk of a first coronary heart disease event. The potential clinical use of this panel of SNPs remains to be defined.The Wellcome Trust; Academy of Finland Center of Excellence for Complex Disease Genetics; US National Institutes of Health; the Donovan Family Foundation.

Dataset Information

Apolipoprotein A5 gene variants and the risk of coronary heart disease: a case?control study and meta?analysis.

Publications

Apolipoprotein A5 gene variants and the risk of coronary heart disease: a case‑control study and meta‑analysis.

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