Heme oxygenase microsatellite polymorphism, oxidative stress, glycemic control, and complication development in type 2 diabetes patients

• Published in: Free radical biology & medicine Vol. 53; no. 1; pp. 60 - 63
• Main Authors: Choi, Siu-Wai, Fai Yeung, Vincent Tok, Benzie, Iris F.F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2012
• Subjects: alleles; antioxidants; biomarkers; blood; Blood Glucose; death; Diabetes Complications - etiology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; Diabetic complications; DNA damage; fasting; Female; Free radicals; Genetic Predisposition to Disease; Genotype; genotyping; glucose; glycemic control; glycohemoglobin; GT repeats; heme oxygenase (biliverdin-producing); Heme oxygenase-1; Heme Oxygenase-1 - genetics; Humans; lipids; Male; microsatellite repeats; Microsatellite Repeats - genetics; Middle Aged; noninsulin-dependent diabetes mellitus; Oxidative Stress; patients; Polymorphism, Genetic - genetics; promoter regions; Promoter Regions, Genetic - genetics; risk; Risk Factors; Type 2 diabetes; Type 2 diabetes; Oxidative stress; Diabetic complications; Free radicals; GT repeats; Heme oxygenase-1
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2012.04.017

Heme oxygenase-1 (HMOX-1) is activated by oxidative stress, and gene responsiveness is reportedly determined by the number of dinucleotide (GT(n)) repeats in its highly polymorphic promoter region. “Short” (S; GT(n)<25) alleles reportedly associate with higher response, lower oxidative stress, lower risk of type 2 diabetes mellitus (type 2DM), and better glycemic control and outcome, but data are conflicting. We investigated GT(n) in type 2DM subjects (all ethnic Chinese) in relation to basal glycemic control, oxidative stress, and outcome during up to 9 years' follow-up. Fasting blood from 418 type 2 DM subjects was collected at entry for GT(n) genotyping, glycated hemoglobin, glucose, lipids, and biomarkers of oxidative stress and antioxidants. A subset (n=368) was followed for up to 9 years for incident complications or death. GT(n) genotype distribution was 128, 182, and 108 for, respectively, S/S, S/L, and L/L. No significant differences in glycemic control, lipids, or oxidative stress were seen across genotypes. During follow-up, 168/368 subjects developed complications. No association was seen with GT(n). No difference in plasma HO-1 was seen between genotypes in a small substudy (S/S n=21 vs L/L n=23). Glycated hemoglobin and lymphocytic DNA damage was higher (p<0.05) at entry in the incident complications group. No other significant differences were seen in oxidative stress or antioxidants. Data do not support the postulated link between HMOX-1 microsatellite polymorphism and type 2 DM or the putative beneficial effect of the S allele on glycemic control, oxidative stress, or outcome in type 2 DM patients, at least in this particular population. ► Activation of polymorphic HMOX-1 by oxidative stress is cytoprotective. ► Promoter GT(n)>25 reportedly blunts activation; this may affect outcome in type 2 diabetes mellitus (T2DM). ► We studied GT(n) and outcome in T2DM patients followed for up to 9 years. ► Oxidative stress and glycemic control were not different across GT(n) genotypes. ► GT(n) did not influence complication development.