Association Analysis of Polymorphism rs386000 of the LILRA3 Gene and the Risk of Atherosclerosis Obliterans: a Pilot Study

Abstract

Aim. To study the association of the rs386000 polymorphic variant in the LILRA3 gene with the risk of developing obliterating atherosclerosis of the lower extremity arteries (OALEA).Material and methods. 1277 individuals of Slavic origin were examined (629 patients with OALEA and 648 healthy volunteers). Genotyping of the LILRA3 gene rs386000 was performed with a MassARRAY-4 genomic mass spectrometer. Polymorphic variants of the LILRA3 gene, that encodes the leukocyte immunoglobulin-like receptor A3, may be attractive objects for studying the mechanisms of atherosclerosis.Results. The study showed that the rs386000 polymorphic variant in the LILRA3 gene was associated with the risk of developing OALEA. However, this association was characterized by sexual dimorphism: in men, carriage of the rs386000-C allele (p=0.03) and the rs386000-C/C genotype (p=0.01) was protective against the risk of developing OALEA, while in women, this polymorphism did not influence the susceptibility to the disease. Single nucleotide polymorphism (SNP) annotation showed that carriage of the rs386000‑C allele was associated with an increased expression of the LILRA2, LILRB5, LILRA6, LILRP1 and TSEN34 genes and a decreased expression of the LILRA3 and LILRA5 genes in the blood.Conclusion. The present study revealed for the first time an association of the rs386000‑C allele of the LILRA3 gene with a reduced risk of developing OALEA. Further studies, including experimental studies, will determine the specific mechanisms mediating the involvement of the LILRA3 gene rs386000 polymorphism in the molecular mechanisms for the development of obliterating atherosclerosis, as well as the nature of the sex-specific association of the polymorphism.