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.
1Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Health Science, Linköping University, Sweden.
Liza U
LU
Ljungberg
Carl Johan
CJ
Östgren
Fredrik H
FH
Nyström
Toste
T
Länne
D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D012083:Renin
Hypertension; T2D; central hemodynamics; gender; rs6693954