Matrix metalloprotease-9 polymorphism and its association with Atherosclerosis - A case-control study in Pakistani population.

Objective: To determine the association of matrix metalloproteinase-9 gene with the onset of atherosclerosis in Pakistani population of Punjabi origin.

Methods: The case-control study was conducted from September 2015 to December 2016 at the Government College University, Lahore, Pakistan, and comprised atherosclerosis cases from the Punjab Institute of Cardiology, Lahore, as well as healthy controls. Single nucleotide polymorphismsrs3918242 (Sph1), rs17577 (Sty1) and rs2274756 (Taq1) were selected from the matrix metalloproteinase-9 gene for allelic and genotypic analysis. Direct sequencing and polymerase chain reaction-restriction fragment length polymorphism were performed for genotypic analysis.

Results: the 201 subjects, 100(49.8%) were controls and 101(50.2%) were cases. There were 75(75%) males among the controls and 70(69.3%) among the cases. Overall mean age of the controls was 47.3}13.1 years, and that of the cases was 59.2}10.2 years. Positive family history was a significant factor risk for atherosclerosis (p<0.05). Allele T and genotype CT and TT of rs3918242 were more frequent in the cases (p<0.05). Change in nucleotide at Sph1 site led towards -1562C >T polymorphism. The frequency of 'A' allele and 'GA' genotype for rs17577 was significantly higher in the cases (Sty1) (p<0.05). No association was detected between rs2274756 (Taq1) and atherosclerosis (p> 0.05). The co-expression of rs17577 and rs2274756 was significantly related with the onset of atherosclerosis (p<0.05). Haplotypes CAG, TAG and TGG were significantly involved in causing atherosclerosis (p<0.05) whereas CGG was protective against atherosclerosis in this population (p<0.05).

Conclusions: Matrix metalloproteinase-9 gene was identified as a susceptible gene for the onset of atherosclerosis in Pakistani population of Punjabi origin.