[Polymorphism rs7692387 of GUCY1A1 as a genetic marker for peripheral artery disease in cigarette smokers]

It is known that polymorphisms at gene encoding GUCY1A1 (α-subunit 1 of guanylate cyclase type 1) are associated with a predisposition to coronary artery disease and arterial hypertension, however, the relationship between these polymorphisms and the risk of peripheral artery disease (PAD) remains unexplored. This pilot study aimed to study the association of two polymorphisms such as rs7692387 and rs13139571 of the GUCY1A1 gene with the risk of peripheral artery disease. The study included 1277 unrelated individuals of Slavic origin, including 629 PAD patients and 648 relatively healthy volunteers. Genotyping of polymorphisms was done by the MassARRAY-4 system. We found that the rs7692387-A allele (OR=1.42, 95% CI 1.17-1.74, p=0.0005) and the rs7692387-G/A-A/A genotypes (OR=1.77, 95% CI 1.28-2.44, p=0.0005) were associated with an increased risk of peripheral artery disease, regardless of sex, age, body mass index, coronary artery disease, and hypertension. In addition, haplotype rs7692387A-rs13139571A (OR=1.52, 95%CI 1.17-1.98, p=0.002) was associated with an increased risk, while haplotype rs7692387G-rs13139571A (OR=0.26, 95%CI 0.12-0.58, p=0.0090), on the contrary, possessed a protective effect against disease risk. However, the observed associations occurred in cigarette smokers. Bioinformatics analysis showed that polymorphism rs7692387 is a functionally significant variant associated with increased GUCY1A1 expression and alternative polyadenylation in the tibial artery as well as a target for transcription factors and epigenetic regulation of gene expression. Thus, polymorphism rs7692387 of the GUCY1A1 gene represents a new genetic variant by which cigarette smoking, a major risk factor for peripheral artery disease, contributes to the disease development.