Clinical Study And Meta - Analysis Of The Association Between Platelet Membrane Glycoprotein Gene Polymorphism And Coronary Heart Disease

Objective:To study the association of platelet membrane glycoprotein polymorphisms(GP I aC807T、GP I bαKOZAK-5T/C、GPⅥT13254/C HPA-1a/b and HPA-2a/b) and CAD (coronary artery disease).Methods:A case-control study design was adopted. The study group consisted of150patients (mean age=63.91±10.45year) with coronary artery disease identified by coronary angiography and153individuals (mean age=64.65±10.80year) without coronary artery disease. A newly-developed technology named improved Multiplex Ligation Detection Reaction, iMLDR, was used to detect target genes and SNPs. Stata12.0was used to analysis results.Results:1) Comparisons of genotype and allele distributions:For GP I aC807T, the results were significant statistically(genotype:X2=6.640, P=0.036, allele:X2=5.725, P=0.017). For GPⅥT13254/C, allele frequencies were different between both groups(P=0.004, Fisher’s exact test), but genotype distributions were not different statistically(P=0.059, Fisher’s exact test). But for GP I baKOZAK-5T/C, HPA-1a/b and HPA-2a/b, the distributions of genotype and allele were not different significantly between cases and controls.2) In a variety of gene analysis models, it was showed that GP I aC807T polymorphism had the greatest influence on CAD in additive model(OR=2.75,95%CI=1.18-6.71), then in recessive model (OR=2.48,95%CI=1.11-5.83) and allele model (OR=1.52,95%CI=1.06-2.17). There was no significant association in dominant model and Co-dominant model. In all gene analysis models, there was no significant association between GP I baKOZAK-5T/C and CAD to be found.3) An association between mutant allele numbers of platelet membrane glycoprotein included in this study and coronary lesion was found by logistic regression analysis(OR=1.36, P=0.008,95%CI=1.082-1.707).4) Even adjusted by gender, blood glucose, fibrinogen, total cholesterol and triglyceride, still logistic analysis showed that TT genotype of GP I aC807T has increased markedly CAD risk than CC genotype (OR=4.00, P=0.020, 95%CI=1.24-12.88).Conclusion:GP I aC807T polymorphism correlates significantly with coronary artery disease, and TT genotype is independent risk factor for coronary artery disease. C allele of GPⅥT13254/C may increase risk for CAD. Associations of GP I baKOZAK-5T/C, HPA-1a/b and HPA-2a/b polymorphisms with CAD have not yet been found. The number of mutant alleles carried by somebody correlate positively with CAD risk. Objective:So far, association between polymorphism of platelet membrane glycoprotein and CAD(Coronary Artery Disease) is still ambiguous on account of prior controversial results from clinical studies. Objective of this study is to evaluate association of polymorphisms of HPA-2a/b(Human Platelet Alloantigen2), GPVIT13254C(GP, Glycoprotein) and GP I baVNTR(Variable Number of Tandem Repeats) with CAD by performing a meta-analysis.Methods:All case-control studies published in English or Chinese whose research purpose is to evaluate association of platelet membrane glycoprotein polymorphism with CAD were retrieved. Electronic databases were searched up to March2014. The pooled odds ratios(ORs) with95%confidence intervals(CIs) were calculated in a variety of genetic models. According to heterogeneity within studies, fixed-effect model or random-effect model was used to analyze outcome data. Source of heterogeneity was detected by meta-regression analysis. Publication bias among studies was tested by funnel plots or Begg’s linear regression.Results:Eventually29independent studies were included into a meta-analysis after excluding some irrelevant studies. The combined results using random-effect model showed some significant associations between HPA-2a/b and CAD(allelic model:OR=1.43,95%CI=1.07-1.91; dominant model:OR=1.57,95%CI=1.08-2.28). There was no significant evidence of association between GPⅥT13254C polymorphisms and CAD(allelic model: OR=1.06,95%CI=0.82-1.37, random-effect model; dominant model:OR=1.11,95%=0.93-1.31, fix-effect model). And in all genetic analysis model, none of association between GP Ⅰ bαVNTR polymorphism and CAD was found.Conclusion:Our present meta-analyses suggested that HPA-2a/b polymorphism contribute to the occurrence and development of CAD. HPA-2b allele and HPA-2ab+bb genotypes may increase the risk for CAD. There may be no association of GPⅥT13254C and GP Ⅰ bαVNTR polymorphisms with CAD. More clinical studies should be needed to comprehensively elaborate the association between platelet glycoprotein polymorphism and CAD in the future.