Galanakis Emmanouil, Kofteridis Diamantis, Stratigi Kalliopi, Petraki Eleni, Vazgiourakis Vassilios, Fragouli Eleni, Mamoulakis Dimitrios, Boumpas Dimitrios T, Goulielmos George N
Department of Paediatrics, University of Crete, Heraklion, Crete, Greece.
Hum Immunol. 2008 Apr-May;69(4-5):279-83. doi: 10.1016/j.humimm.2008.03.001. Epub 2008 Apr 1.
Current classifications of diabetes distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D), however recent evidence highlights overlap between T1D and T2D. Earlier studies have suggested altered nitric oxide (NO) metabolism in both T1D and T2D. In the present case-control study, we investigated whether the endothelial NO synthase gene intron 4 a/b polymorphism is associated with T1D and T2D in the island of Crete, a well-defined area with genetically homogeneous population. Mutated allele "a" was more common in individuals with both T1D and T2D than in controls (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.06-2.77, p = 0.013; and OR = 1.50, 95% CI = 0.930-2.42, p = 0.047, respectively). Mutated genotype (a/a or a/b) was more common in individuals with T1D than in nondiabetic individuals (OR = 1.93, 95% CI = 1.12-3.32, p = 0.008); this increased frequency was also observed for T2D, although not at a significant level (OR = 1.38, 95% CI = 0.802-2.37). No difference was found in the frequency of mutated allele a or mutated genotype (a/a or a/b) between T1D and T2D populations. In conclusion, our results indicate that allele a of the intron 4 endothelial NO synthase gene is associated with susceptibility to both T1D and T2D and may represent a common genetic factor for diabetes.
目前糖尿病的分类区分了1型糖尿病（T1D）和2型糖尿病（T2D），然而最近的证据凸显了T1D和T2D之间的重叠。早期研究表明，T1D和T2D中一氧化氮（NO）代谢均发生改变。在本病例对照研究中，我们调查了内皮型NO合酶基因内含子4 a/b多态性是否与克里特岛的T1D和T2D相关，克里特岛是一个人口基因同质化的明确区域。在患有T1D和T2D的个体中，突变等位基因“a”比对照组更为常见（优势比[OR]=1.71，95%置信区间[CI]=1.06 - 2.77，p = 0.013；以及OR = 1.50，95% CI = 0.930 - 2.42，p = 0.047）。突变基因型（a/a或a/b）在患有T1D的个体中比非糖尿病个体更为常见（OR = 1.93，95% CI = 1.12 - 3.32，p = 0.008）；T2D也观察到这种频率增加，尽管未达到显著水平（OR = 1.38，95% CI = 0.802 - 2.37）。在T1D和T2D人群之间，突变等位基因a或突变基因型（a/a或a/b）的频率未发现差异。总之，我们的结果表明，内含子4内皮型NO合酶基因的等位基因a与T1D和T2D的易感性相关，可能代表糖尿病的一个共同遗传因素。
