Genetic Polymorphisms Associated with Iliac Artery Calcification in Peripheral Artery Disease

Vascular calcification is an active, genetically regulated process linked to adverse outcomes. While most genetic studies have examined coronary artery calcification, little is known about peripheral arteries. We investigated the association between selected single nucleotide polymorphisms (SNPs) and iliac artery calcification in patients with peripheral artery disease (PAD).

This single-center case-control study included 49 PAD patients who underwent computed tomography angiography. Iliac calcification was quantified using the Agatston-based iliac calcium score (ICS). Patients were classified as low/absent (<100 AU) or high (≥100 AU). Clinical variables and SNPs related to lipid metabolism and vascular calcification (rs10902661, rs11164798, rs347152, rs9381256, rs6569979, rs7023109, rs11024756, rs11062625) were analyzed. Genotyping was performed with the KASP™ system, and logistic regression models were adjusted for conventional risk factors.

Mean age was 66.3 ± 9.4 years, and 85.7% were male. Patients with high ICS more often had diabetes mellitus (48.1% vs. 22.7%; P = 0.04) and chronic kidney disease (29.6% vs. 9.1%; P = 0.03). Among SNPs, rs10902661 showed the strongest association: the C:T genotype was less frequent in the high ICS group (14.8% vs. 45.5%; P = 0.01) and was linked to lower odds of high ICS (odds ratio, 0.22; 95% confidence interval, 0.06-0.84; P = 0.026). The model including rs10902661 showed modest discrimination (area under the curve = 0.68).

Rs10902661 may act as a protective genetic factor against iliac artery calcification, highlighting heterogeneity across vascular beds. Replication in larger cohorts is needed to confirm these findings and assess clinical implications in PAD.