Contribution of Genetic Polymorphism in the Renin–Angiotensin System to the Development of Renal Complications in Insulin-dependent Diabetes
نویسندگان
چکیده
Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system—angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor—and the renal involvement of insulindependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine $ 150 m mol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: x 2 for trend 5.135, P 5 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209–2.952, P 5 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly ( P 5 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients. ( J. Clin. Invest. 1997. 99:1585–1595.)
منابع مشابه
Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus.
OBJECTIVE Patients with insulin-dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascular diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among populations. METHODS In 257 Dutch IDDM patients (188 with urinary albumin excretion (UAE) <30 mg/24 h)...
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