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Background: Via sequencing the genes of apelin/angiotensin receptor-like 1 (apelin/APJ) pathway, we have recently identified and validated four common polymorphisms (rs3761581, rs56204867, rs7119375, and rs10501367) implicated in the development of hypertension. Extending these findings, we, in Chinese hypertensive patients, sought to investigate the association of these four polymorphisms and one additional promising candidate (rs9943582) from this pathway with the risk of developing coronary artery disease (CAD). Methodology/Principal Findings: Genotypes were obtained from 994 sporadic CAD patients and 708 age- and sex-matched controls. All participants were hypertensives and angiographically-confirmed. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares. Genotype distributions of five examined polymorphisms satisfied Hardy-Weinberg equilibrium in controls of both genders. Single-locus analyses exhibited no significant differences in the genotype/allele frequencies of examined polymorphisms between CAD patients and controls (P>0.05), even after controlling traditional cardiovascular confounders. In haplotype analyses, low-penetrance haplotype G-A (in order of rs56204867 and rs3761581 from apelin gene) was significantly overrepresented in controls (1.73%) relative to in CAD patients (0.4%) in males (P = 0.047). Further interaction analyses suggested an overall best MDR model including rs3761581 in males (P = 0.0408) and including rs7119375 and rs9943582 in females (P<0.0001), which were further substantiated in the classical logistical regression model. Conclusions: Our findings demonstrated a contributive role of low-penetrance haplotype in apelin gene on CAD in males, and more importantly, interactive effects of genetic defects in apelin/APJ pathway might confer a potential risk in Chinese hypertensive patients. [ABSTRACT FROM AUTHOR]

Background: Contradictory results have been reported regarding the association between Pro12Ala polymorphism of PPARc2 and coronary artery disease (CAD). We sought to estimate the inconsistent results by performing a comprehensive meta-analysis. Methods: Studies in English or Chinese publications were identified by screening MEDLINE, Embase, CNKI, Wanfang and CBM. 22 studies including 8948 cases and 14427 controls were selected. A random-effects model was applied to combine the divergent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias. Results: The Pro12Ala polymorphism of control population followed Hardy-Weinberg equilibrium for all studies (P=0.05). Overall, a marginal increased risk of CAD under the recessive genetic model (AlaAla vs ProAla+ProPro: P = 0.04, OR = 1.31, 95%CI 1.01-1.69, Pheterogeneity = 0.67, I2 = 0%) and the homozygote comparison (AlaAla vs ProPro: P = 0.04,OR = 1.30, 95%CI 1.01-1.68, Pheterogeneity = 0.68, I2 = 0%) was observed. In the subgroup analysis by ethnicity, carriers of AlaAla homozygotes had a significant increased risk for CAD among Caucasians (AlaAla vs ProAla+ProPro: P = 0.01, OR = 1.45, 95%CI 1.08-1.96, Pheterogeneity = 0.48, I2 = 0%; AlaAla vs ProPro: P = 0.02,OR = 1.44, 95%CI 1.07-1.93, Pheterogeneity = 0.46, I2 = 0%). After dividing into population source, the CAD risk magnitude of hospital-based studies was distinctly strengthened under the recessive model (P = 0.03,OR = 1.85,95%CI 1.07-3.19, Pheterogeneity = 0.87,I2 = 0%) and the homozygote comparison (P = 0.03,OR = 1.83, 95%CI 1.06-3.16, Pheterogeneity = 0.88, I2 = 0%). There was no observable publication bias as reflected by funnel plot and Egger's linear regression test (t = -0.12, P = 0.91). Conclusion:: Our results demonstrated that the PPAR γ2 Pro12Ala polymorphism might be risk-conferring locus for the progression of CAD among Caucasians, but not among Asians. [ABSTRACT FROM AUTHOR]

Background: Coronary artery disease (CAD) is the most common heart disease worldwide. Association of CAD with variants in the myocyte enhancer factor 2A (MEF2A) gene, the first identified CAD-causing gene, has attracted special attention but the results are controversial. We aimed to evaluate this genetic association via a case-control study and meta-analysis. Methodology/Principal Findings: We performed a case-control association study to investigate the relationship between variations in exon 11 of MEF2A gene and CAD in 1045 sporadic patients and 1008 controls enrolled angiographically among southern Chinese population, and then the data from this study were compared and discussed in a systematic review and meta-analysis with all available published studies on MEF2A gene and CAD. In total, eight variants were identified (21-bp deletion, CAG repeats, CCG repeats, a CCA deletion and four SNPs). No significant link was observed between the common (CAG)n polymorphism and CAD, whereas the rare 21-bp deletion was detected only in five affected individuals. The metaanalysis of (CAG)n polymorphism and CAD risk, including nine studies with 3801 CAD patients and 4020 controls, also provided no convincing evidence for the genetic association, even upon stratification by race (mainly Whites and Chinese). However, the 21-bp deletion was regarded as a potentially logical, albeit undetermined, candidate for CAD in the following systematic review. Conclusions/Significance: Our findings failed to demonstrate a correlation between (CAG)n polymorphism with CAD, however, we concluded that the rare 21-bp deletion might have a more compelling effect on CAD than the common (CAG)n polymorphism, and MEF2A genetic variant might be a rare but specific cause of CAD/MI. [ABSTRACT FROM AUTHOR]