Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis

Abstract

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.

Keywords: APOC3; Coronary heart disease; Meta-analysis; Polymorphism.

Figure 1.

Flow diagram of the study identification.

Figure 2.

Forest plot of the association between the APOC3 SstI polymorphism and CHD under the allelic contrast model (S2 vs. S1). The horizontal lines correspond to the study-specific OR and 95% CI, respectively. The area of the squares reflects the study-specific weight. The diamond represents the pooled results of the OR and the 95% CI.

Figure 3.

Forest plot of the association between the APOC3 T-455C polymorphism and CHD under the allelic contrast model (C vs. T). The horizontal lines correspond to the study-specific OR and 95% CI. The area of the squares reflects the study-specific weight. The diamond represents the pooled results of the OR and the 95% CI.

Figure 4.

Forest plot of the association between the APOC3 C-482T polymorphism and CHD under the allelic contrast model (T vs. C). The horizontal lines correspond to the study-specific OR and 95% CI. The area of the squares reflects the study-specific weight. The diamond represents the pooled results of the OR and the 95% CI.

Figure 5.

Funnel plot for the publication bias tests. Each point represents a separate study for the indicated association. The horizontal and vertical axis correspond to the OR and confidence limits (OR: odds ratio, SE: standard error). A: SstI polymorphism under the allelic contrast model (S2 vs. S1); B: T-455C polymorphism under the allelic contrast model (C vs. T); C: C-482T polymorphism under the allelic contrast model (T vs. C).