Association of the ITGA4 rs1143674 polymorphism with subclinical atherosclerosis in patients with ulcerative colitis over 40 years of age
Background: Patients with ulcerative colitis (UC) have an increased cardiovascular risk due to chronic inflammation and endothelial dysfunction. The ITGA4 gene encodes the α4 integrin subunit, a key regulator of leukocyte adhesion to endothelium. The ITGA4 rs1143674 genetic variant has been associated with coronary atherosclerosis and myocardial infarction, while its homozygous CC genotype is linked to severe UC course. However, data on the association of the ITGA4 rs1143674 variant with subclinical atherosclerosis in UC patients are lacking in the literature, and the impact of age on the manifestation of this genetic risk has not been evaluated. Aim: To determine the association of the ITGA4 rs1143674 genetic variant with subclinical atherosclerosis of the carotid and femoral arteries in UC patients according to age. Methods: A single-center, observational, cross-sectional, comparative study was conducted. From March 2023 to December 2025, UC patients and healthy volunteers underwent clinical examination, ultrasound examination of the carotid and femoral arteries, and molecular genetic testing. Subclinical atherosclerosis was defined as carotid intima-media thickness 0.9 mm or the presence of an atherosclerotic plaque in at least one vascular bed. Atherosclerotic plaques were defined as a focal thickening of the vessel wall exceeding 50% compared to adjacent areas, or a focal thickening 1.5 mm protruding into the arterial lumen. Genotyping of the ITGA4 rs1143674 polymorphism was performed by real-time polymerase chain reaction. Results: The main group included 111 UC patients (median age 40.0 [33.3; 47.0] years, 50 (45%) males); the control group comprised 73 healthy volunteers (median age 40.0 [32.3; 49.0] years, 26 (35.6%) males). Subclinical atherosclerosis was identified in 61 (54.9%) UC patients, which was 2.4 times more frequent than in the control group (odds ratio (OR) 4.02; 95% confidence interval (CI) 2.08–7.77; p = 0.001). The prevalence of atherosclerosis in the 20–40 years age group was 38.9% (21/54), and in the 41–60 years age group was 70.2% (40/57) (OR 3.7; 95% CI 1.68–8.13; p = 0.001). The genotype distribution of ITGA4 (rs1143674) in the UC group did not differ from that in the control group (p = 0.793). In the overall UC cohort, no association between the genotype and atherosclerosis was found (p = 0.260). After age stratification, no differences in genotype frequencies were observed between patients with and without atherosclerosis in the 20–40 years age group (p = 0.705); in the 41–60 years age group, the homozygous CC genotype was more frequent in patients with atherosclerosis than in those without (30% (12/40) vs 5.9% (1/17), p = 0.039). Multivariable logistic regression analysis showed that age 40 years (OR 6.73; 95% CI 2.52–17.92; p 0.001), the CC genotype of ITGA4 rs1143674 (OR 3.09; 95% CI 1.11–8.64; p = 0.031), and chronic continuous UC course (OR 5.77; 95% CI 2.14–15.56; p = 0.001) were independent predictors of atherosclerosis. The developed prognostic model demonstrated acceptable discriminatory performance: AUC 0.761 (bootstrap-verified 95% CI 0.689–0.847). Conclusion: In patients with UC, the homozygous ITGA4 rs1143674 CC genotype is associated with subclinical atherosclerosis only in those aged over 40 years. The proposed prognostic model for atherosclerosis development, including age 40 years, continuous UC course, and the CC genotype of ITGA4 rs1143674, may be used for cardiovascular risk stratification and to justify early instrumental screening in carriers of the unfavorable genotype.