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Background  Increased activation of the renin-angiotensin system (RAS) may be important in promoting coronary heart disease (CHD) and renal dysfunction, but limited data are available on associations between angiotensin type 1 receptor ( AGT1R ) and angiotensinogen ( AGT ) genotypes in type 2 diabetes.    Methods  Study participants were diabetics from the Health Professionals Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). We analyzed single nucleotide polymorphisms (SNPs) associated with cardiovascular pathophysiology (including  AGT1R  T573C,  AGT1R  A1166C, and  AGT  M235T) and presence of renal dysfunction (eGFR<60 ml/min/1.73 m 2 ) or history of CHD.    Results  The  AGT1R  1166 C-allele was associated with eGFR<60 ml/min/1.73 m 2  (multivariable OR 1.63 [1.01, 2.65]) in the HPFS men (n = 733) and in the combined dataset (n = 1566) (OR 1.42 [1.02, 1.98]). The  AGT1R  1166 C-allele was also associated with CHD in men (OR 1.57 [1.10, 2.24]). In NHS women (n = 833),  AGT  235T-allele was associated with CHD (OR 1.72 [1.20, 2.47]). Removal of hypertension from the fully adjusted models did not influence results, suggesting that the associations may not be mediated by hypertension. There were significant interactions between sex and  AGT1R  1166 C-allele (p = 0.008) and  AGT  M235T (p = 0.03) in models for CHD. No significant associations were seen between  AGT1R  T573 C-allele and renal dysfunction or CHD.    Conclusion  Polymorphisms in  AGT1R  and  AGT  genes are associated with renal dysfunction and CHD in type 2 diabetes and further support the important role of the RAS in these complications. Sex may modify associations between  AGT1R  1166 C-allele and  AGT  235T and CHD in type 2 diabetes.

bmc nephrology

Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus