An association study of thrombospondin 1 and 2 SNPs with coronary artery disease and myocardial infarction among South Indians

Introduction

Thrombospondin 1 and 2 are multidomain calcium-binding extracellular glycoproteins and they play a role in platelet aggregation, inflammatory response and assembly of connective tissue extracellular matrix. The association of thrombospondins (TSP) in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) is well established. The association of the TSP-1 (Asn700Ser, 2210A → G, rs2228262) and TSP-2 un-translated region (UTR) (3949 T → G, rs8089) gene variations among South Indian CAD and MI patients has been examined in the present study.

Materials and Methods

We analyzed the thrombospondin polymorphisms in unrelated CAD patients (n = 511) and a subgroup with an event of MI (n = 173) compared with controls (n = 522). The polymorphisms were assessed using polymerase chain reaction, restriction fragment length analysis and the circulating TSP concentration were measured using enzyme linked immune-sorbent assay.

Results

The prevalence of TSP-1 and TSP-2 alleles did not show any significant difference statistically, when compared controls against CAD/MI patients. The rare GG genotype of the N700S polymorphism was not observed among the studied population. Further, multiple regression analysis revealed that there was no significant risk for CAD (OR = 1.68; 95% CI 0.927 - 3.055; p = 0.087) or MI (OR = 1.84; 95% CI 0.846 - 4.007; p = 0.124) for the GA genotype. The GA genotype showed no impact on clinical characteristics of the CAD patients and their circulating TSP-1 levels. A similar non-association was observed for the TSP-2 in 3949 T → G polymorphism (GG genotype) for CAD (OR = 0.64; 95% CI 0.278 - 1.455; p = 0.636) and MI (OR = 0.53; 95% CI 0.166 - 1.675; p = 0.278).

Conclusions

Our data suggests that the presence of thrombospondin-1 (rs2228262) and thrombospondin-2 (rs8089) variants need not be considered a risk for coronary artery disease or myocardial infarction among South Indians.