Lipid-associated GWAS loci as important markers of the risk, severity, and clinical course of peripheral artery disease.

Background: This study investigated the relationship between lipid-associated loci identified through genome-wide association studies (GWAS) and the risk of peripheral artery disease (PAD), its severity, as well as clinical and laboratory features.

Research design and methods: A study included 1263 unrelated Russian subjects, consisting of 620 patients diagnosed with PAD and 643 healthy controls. Thirteen single nucleotide polymorphisms (SNP) were genotyped using the MassArray-4 system.

Results: Polymorphisms rs1689800, rs55730499 and rs881844 were found to be associated with an increased risk of PAD, whereas SNPs rs1883025, rs3136441, rs3764261 and rs6065906 showed protective effects against disease (P_perm ≤ 0.05). SNPs rs1689800, rs217406, rs1883025, and rs3136441 exhibited combined effects with cigarette smoking on the PAD risk (P_perm ≤ 0.05). Polymorphisms rs55730499 (beta = 0.124, P_perm = 0.04), rs9987289 (beta = 0.558, P_perm = 0.03), and rs881844 beta = -0.171, P_perm = 0.03) correlated with the ankle-brachial index. Multiple associations have been found between the SNPs and clinically significant characteristics, including disease severity, risk of gangrene, early disease onset, plasma procoagulant and atherogenic lipid changes (P_perm ≤ 0.05).

Conclusions: We identified novel genetic markers associated with PAD susceptibility and disease-related clinical and laboratory features. The identified biomarkers enhance the potential for predictive genetic testing related to the risk and progression of PAD, facilitating the integration of molecular diagnostics into clinical decision-making processes.