Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
Free Radic Biol Med. 2012 Jul 1;53(1):60-3. doi: 10.1016/j.freeradbiomed.2012.04.017. Epub 2012 Apr 25.
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.
血红素加氧酶-1（HMOX-1）可被氧化应激激活，其基因反应性据报道取决于高度多态启动子区域中的二核苷酸（GT(n)）重复数。“短”（S；GT(n)<25）等位基因据称与更高的反应性、更低的氧化应激、更低的 2 型糖尿病（2 型 DM）风险以及更好的血糖控制和结果相关，但数据存在矛盾。我们研究了 2 型 DM 患者（均为华裔）中与基础血糖控制、氧化应激和长达 9 年随访期间结果相关的 GT(n)。418 例 2 型 DM 患者在入组时采集空腹血样进行 GT(n)基因分型、糖化血红蛋白、血糖、脂质以及氧化应激和抗氧化剂的生物标志物检测。一个亚组（n=368）随访长达 9 年，以检测新发并发症或死亡。GT(n)基因型分布分别为 S/S、S/L 和 L/L，频率分别为 128、182 和 108。各基因型间的血糖控制、脂质或氧化应激无显著差异。随访期间，168/368 例患者发生并发症。GT(n)与并发症无相关性。小型亚研究中，各基因型间血浆 HO-1 无差异（S/S n=21 与 L/L n=23）。新发并发症组患者的糖化血红蛋白和淋巴细胞 DNA 损伤更高（p<0.05）。氧化应激或抗氧化剂无其他显著差异。数据不支持 HMOX-1 微卫星多态性与 2 型 DM 之间的假定联系，也不支持 S 等位基因对 2 型 DM 患者血糖控制、氧化应激或结果的假定有益作用，至少在该特定人群中是如此。
