Beyond Traditional Risk Factors: The Role of the CYP11B2 C(-344)T Polymorphism in Atherosclerosis and Cardiorenal Syndrome Phenotypes in Diabetes Mellitus

Background: This study aimed to evaluate the association of the CYP11B2 C(-344)T polymorphism with cardiorenal phenotypes and atherosclerosis in patients with DM. Methods: A total of 269 patients with DM (180 with type 2 and 89 with type 1 diabetes) and 50 age-matched controls without DM were included in this study. Clinical, laboratory, echocardiographic, and vascular parameters were assessed, and CYP11B2 genotyping was performed by allele-specific PCR. Results: The T allele and TT genotype were significantly more frequent in patients with DM than in controls (64% and 47% vs. 48% and 26%, respectively) and were associated with adverse cardiorenal phenotypes. TT carriers also showed higher levels of homocysteine and fibroblast growth factor-23, as well as worse renal and vascular parameters. In multivariable analysis, the TT genotype was independently associated with higher odds of chronic kidney disease (OR 12.21, 95% CI 3.76–39.61), heart failure (OR 3.80, 95% CI 1.67–8.66), left ventricular hypertrophy (OR 2.17, 95% CI 1.02–4.59), and atherosclerosis (OR 2.33, 95% CI 1.02–5.32). Conclusions: The CYP11B2 C(-344)T polymorphism, particularly the TT genotype, was associated with increased risk of diabetic cardiorenal and atherosclerotic complications. These findings suggest that aldosterone synthase gene variation may contribute to diabetic cardiorenal and vascular complications and may be useful for future risk-stratification research.