Heme oxygenase-1 (HO-1) catalyzes the conversion of heme to carbon monoxide, free iron, and biliverdin, which is then changed into bilirubin. These substances have been recently demonstrated to have antiatherogenic and antioxidative properties. The GT-repeat polymorphism is reported to be an independent risk factor for restenosis after coronary stenting and T (−413). A polymorphism increased the activity of HO-1 promoter, leading to reduce the incidence of ischemic heart disease in Japanese population. The aim of the present study was to investigate association between polymorphisms in the promoter of HO-1 and the prevalence of vascular complications in type 2 diabetic (T2DM) patients.
We genotyped rs2071746 (−413T/A) and rs3761439 (−1135G/A) in the promoter region of HO-1 in 601 T2DM patients. Clinical and biochemical parameters were measured and random urine albumin and creatine ratio or 24 h urine analysis were performed to diagnose diabetic nephropathy. The extent of atherosclerosis was determined by the measuring intima-media thickness (IMT) of carotid artery with B-mode ultrasound.
The TT genotype of rs2071746 was associated with high prevalence of nephropathy (odds ratio (OR)=1.58, 95% CI=1.092.29, P=0.016) comparing to the AA+AT genotypes. Patients with AA allele of rs3761439 had increased IMT than subjects with AG+GG alleles (0.883 vs 0.761 mm, P=0.002). The OR of the TT genotype for the presence of carotid plaques in lower BMI (<25) groups was 1.746 (AA+AT versus TT, CI=1.0083.026, P=0.043).
The T(−413)A and G(−1135)A polymorphisms in the promoter of HO-1 have associations with the risk of diabetic nephropathy and subclinical atherosclerosis in T2DM patients, respectively.
25 - 29 Apr 2009
European Society of Endocrinology