Associations of genetic polymorphisms in the renin-angiotensin system with central aortic and ambulatory blood pressure in type 2 diabetic patients

Patients with type 2 diabetes (T2D) are at high risk of developing hypertension and related cardiovascular disease. The renin-angiotensin system (RAS) plays a central role in regulation of blood pressure (BP). Accordingly, each component of this system represents a potential candidate in the etiology of hypertension. This study investigated the impact of polymorphisms within the RAS on ambulatory and central BP in T2D subjects. A cohort of 761 subjects (55-65 years) with T2D was studied. Ambulatory and central BP were measured, and ACE I/D genotype, angiotensinogen M235T, renin rs6693954 and ATR1-A1166C polymorphisms were analyzed. Women carrying the AA-genotype had lower 24-hour and day-time systolic and diastolic BP (p<0.05), and lower night-time and central diastolic BP (p<0.05), compared to T allele carriers. In men, the AA-genotype was instead associated with higher central diastolic BP (p=0.018) and higher augmentation index (p=0.016). Further, the associations between the renin rs6693954 SNP and diastolic BP were strongly gender dependent (p≤0.001). In T2D patients, there is a gender-dependent association of the renin rs6693954 SNP with central and ambulatory BP. Women carrying the renin rs6693954 AA-genotype may be protected against the higher BP seen in men with the same genotype.