The Joint Link of the rs1051730 and rs1902341 Polymorphisms and Cigarette Smoking to Peripheral Artery Disease and Atherosclerotic Lesions of Different Arterial Beds
Sergey Zhabin,
Victor Lazarenko,
Iuliia Azarova,
Elena Klyosova,
Marina Bykanova,
Svetlana Chernousova,
Daniil Bashkatov,
Ekaterina Gneeva,
Anna Polonikova,
Mikhail Churnosov,
Maria Solodilova,
Alexey Polonikov
Affiliations
Sergey Zhabin
Department of Surgical Diseases №1, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Victor Lazarenko
Department of Surgical Diseases of Institute of Continuing Education, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Iuliia Azarova
Department of Biological Chemistry, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Elena Klyosova
Laboratory of Biochemical Genetics and Metabolomics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya St., Kursk 305041, Russia
Marina Bykanova
Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya St., Kursk 305041, Russia
Svetlana Chernousova
Department of Surgical Diseases №1, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Daniil Bashkatov
Department of Surgical Diseases №1, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Ekaterina Gneeva
Department of Surgical Diseases №1, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Anna Polonikova
Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Mikhail Churnosov
Department of Medical Biological Disciplines, Belgorod State University, 85 Pobedy Street, Belgorod 308015, Russia
Maria Solodilova
Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Alexey Polonikov
Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
Genome-wide association studies (GWAS) have discovered numerous single nucleotide polymorphisms (SNP) contributing to peripheral artery disease (PAD), but their joint effects with risk factors like cigarette smoking (CS) on disease susceptibility have not been systematically investigated. The present study looked into whether CS mediates the effects of GWAS loci on the development of PAD and atherosclerotic lesions in different arterial beds. DNA samples from 1263 unrelated individuals of Slavic origin including 620 PAD patients and 643 healthy subjects were genotyped by the MassArray-4 system for rs1051730, rs10134584, rs1902341, rs10129758 which are known as PAD-associated GWAS loci. The rs1051730 polymorphism was strongly associated with an increased risk of PAD (p = 5.1 × 10−6), whereas rs1902341 did not show an association with disease risk. The rs1051730 polymorphism was associated with increased plasma levels of LDL cholesterol (p = 0.001), and conferred a greater risk of PAD in cigarette smokers than in nonsmokers (p < 0.01). Interestingly, the rs1902341T allele was associated with an increased risk of PAD in smokers and a decreased disease risk in nonsmokers. SNPs and CS were both linked to unilateral and/or bilateral atherosclerotic lesions of peripheral vessels, as well as the abdominal aorta, coronary, and cerebral arteries. The studied polymorphisms exert pleiotropic and cigarette smoking-mediated effects on atherosclerotic lesions of different arterial beds.
