Association between single nucleotide polymorphisms in thrombospondins genes and coronary artery disease: A meta-analysis.

Objective: This study aimed to assess the association between single nucleotide polymorphisms in thrombospondin-1 (THBS1), thrombospondin-2 (THBS2), thrombospondin-4 (THBS4) and coronary artery disease (CAD) risk.

Methods: Electronic databases were searched before June, 2014 to obtain articles associated with thrombospondin polymorphisms and CAD risk. After identifying case-control studies, odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool effect sizes. Different effect models were used according to heterogeneity. Meta-regression and sensitivity analyses were performed to examine the heterogeneity source. Begg's funnel plot and Egger's test were conducted for publication bias.

Results: 13 studies involving 10,801 cases and 9,381 controls were included. Associations were observed between the THBS1 N700S polymorphism and CAD risk in general population(heterozygote model: OR=1.14, 95% CI: 1.03-1.26; dominant model: OR=1.13, 95% CI: 1.00-1.29), European population (heterozygote model: OR=1.13, 95% CI: 1.00-1.27) and Asian population (heterozygote model: OR=1.57, 95% CI: 1.01-2.44; dominant model: OR=1.56, 95% CI: 1.00-2.43). The THBS2 3' untranslated region (UTR) polymorphism and THBS4 A387P polymorphism were not associated with overall CAD risk. However, an association was observed between the THBS4 A387P polymorphism and CAD risk in the American population (allele model: OR=1.09, 95% CI: 1.00-1.18; homozygote model: OR=1.29, 95% CI: 1.04-1.61; recessive model: OR=1.27, 95% CI: 1.02-1.58).

Conclusions: The THBS1 N700S polymorphism was associated with increased CAD risk, especially in Asian and European populations. No association was observed between the THBS2 3' UTR polymorphism and CAD risk. The THBS4 A387P polymorphism was associated with increased CAD risk in the American population.