Patterns of Thrombospondin Genes Polymorphisms in Acute Myocardial Infarction Patients in Ismailia City

Abstract

Thrombospondin (TSP) 2 and 4 are multidomain calcium-binding extracellular glycoproteins which play a role in platelet aggregation and inflammatory response. TSP-2 has chemotactic and mitogenic activities for vascular smooth muscle cells while TSP-4 mRNA is expressed by endothelial and smooth muscle cells in vascular wall, and brain endothelial cells produce the protein both in vivo and in cell culture, localization consistent with its pro-atherogenic effects. These common functions may be central to the roles of the thrombospondins in coronary artery disease and myocardial infarction (MI). In the present study, the association of the TSP-2 (3949 TG, rs8089) and TSP-4 (Ala387Pro 1186 GC, rs1866389) gene variations and MI among Egyptian patients living in Ismailia city has been examined. Both rs8089 and rs1866389 were studied in 50 acute MI patients and 50 controls using Real-Time polymerase chain reaction. The
prevalence of TSP-2 and TSP-4 alleles was not different in MI patients compared to controls (P> 0.05). Although the minor allele homozygotes (GG) of TSP-2 seems to confer reduced risk of MI (OR: 0.42 95% CI=0.095-1.89) this was not statistically significant (P> 0.05). The distribution of different TSP-4 genotypes did not differ between MI patients and controls (P>0.05).Total cholesterol was statistically significantly higher (P=0.02) in carriers of minor allele (C) of TSP4 (GC+CC). Although, both polymorphisms showed no statistically significant difference in MI patients regarding all other measured conventional risk factors. However, the frequency of TTGC haplotype is statistically significantly higher in MI  patients (24%) than in controls (6%) [P value=0.0226]. Our data suggests that although association analysis with MI did not reach significance, an at-risk haplotype of common variants located in THBS2 and THBS4 may be
part of the genetic determinants for MI in the Egyptian population living in Ismailia city.

Keywords: Myocardial infarction, Thrombospondins