Abstract
BackgroundContradictory results have been reported regarding the association between Pro12Ala polymorphism of PPARγ2 and coronary artery disease (CAD). We sought to estimate the inconsistent results by performing a comprehensive meta-analysis.MethodsStudies 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.ResultsThe 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 PPARγ2 Pro12Ala polymorphism might be risk-conferring locus for the progression of CAD among Caucasians, but not among Asians.
Highlights
Coronary artery disease (CAD) and myocardial infarction (MI), the leading causes of morbidity and death in industrialized countries, represent heavy economic and social burdens on the public health system
The most common gene polymorphism in human Peroxisome Proliferator-Activated Receptor Gamma-2 Gene (PPARc2) gene is cytosine-guanine exchange in exon B which results proline to alanine (Pro12Ala) substitution in the protein [6].The Pro12Ala polymorphism was first identified by Yen et al [7] in 1997 and regarded to reduce transcriptional activity of PPARc2 [8], resulting in lower transcription levels of target genes [9],including tumor necrosis factor a (TNF a), leptin, resistin, adiponectin, and plasminogen activator in hibitor-1(PAI-1), which play important roles in the process of inflammation and atherosclerosis
The following constraints were applied to the search: (1) Articles published in English or Chinese journals or their supplements; (2) Studies in human subjects without country restrictions; (3) When studies from the same research group with overlapped population were found, only the one with largest population was included to avoid data duplication; (4) Have available genotype frequency; (5) If articles containing more than one geographic or ethnic heterogeneous group, each group was treated separately; (6) genotype distribution of control population must be consistent with Hardy-Weinberg equilibrium (HWE)
Summary
Coronary artery disease (CAD) and myocardial infarction (MI), the leading causes of morbidity and death in industrialized countries, represent heavy economic and social burdens on the public health system. There are evidences that the resulting mutant transcription factor profoundly affects the energy metabolism and energy balance and is associated with the risks of atherogenesis [10,11,12] and diabetes [13,14]. Many studies have been performed to explore the association between PPARc2 Pro12Ala polymorphism and CAD, but data are inconsistent [18,19,20,21,22,23]. To derive a more precise estimation, we performed a meta- analysis of published studies to date in order to evaluate the association of PPARc2 gene Pro12Ala polymorphism with CAD, while addressing between-study heterogeneity and publication bias. 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
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