Functional polymorphism rs189037 in the promoter region of ATM gene is associated with angiographically characterized coronary stenosis

Abstract: Objectives: To evaluate the association between the single nucleotide polymorphism rs189037 of the ataxia-telangiectasia mutated (ATM) gene and angiographically characterized coronary stenosis as well as the molecular basis of this association. Results: In 562 patients treated at the Department of Cardiology, West China Hospital, a significant association was found between polymorphism rs189037 and angiographically characterized coronary stenosis. For the T versus C allele, the adjusted OR was 0.79 (95%CI 0.67–0.92, P =0.003), using the allele frequency model; for TT versus CT/CC, the adjusted OR was 0.36 (95%CI 0.21–0.59, P =0.00006), using the recessive model; and for TT/CT versus CC, the adjusted OR was 0.54 (95%CI 0.29–1.02, P =0.06), using the dominant model. An antagonism was found between polymorphism rs189037 and diabetes mellitus (P =0.003). In coronary artery disease (CAD) patients, the TT genotype of rs189037 was associated with higher ATM mRNA expression (F =4.23, P =0.02) in peripheral mononuclear cells than the CC or CT genotypes. Conclusion: Polymorphism rs189037 may influence the expression of ATM mRNA in CAD patients. It is also associated with the degree of coronary stenosis. Moderately low expression of the ATM gene may be associated with the development of coronary atherosclerosis. [Copyright &y& Elsevier]