کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1908843 | 1046687 | 2012 | 4 صفحه PDF | دانلود رایگان |

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 2 DM), and better glycemic control and outcome, but data are conflicting. We investigated GT(n) in type 2 DM 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.
Journal: Free Radical Biology and Medicine - Volume 53, Issue 1, 1 July 2012, Pages 60–63