Prudente Sabrina, Morini Eleonora, Lucchesi Daniela, Lamacchia Olga, Bailetti Diego, Mercuri Luana, Alberico Federica, Copetti Massimiliano, Pucci Laura, Fariello Stefania, Giusti Laura, Cignarelli Mauro, Penno Giuseppe, De Cosmo Salvatore, Trischitta Vincenzo
Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
Department of Experimental Medicine, Sapienza University, Rome, Italy.
Diabetes. 2014 Sep;63(9):3135-40. doi: 10.2337/db13-1966. Epub 2014 Jun 19.
This study tried to replicate in a large sample of white patients with type 2 diabetes (T2D) from Italy a previously reported association of the IRS1 G972R polymorphism with failure to oral antidiabetes drugs (OAD). A total of 2,409 patients from four independent studies were investigated. Case subjects (n = 1,193) were patients in whom, because of uncontrolled diabetes (i.e., HbA1c >8%), insulin therapy had been added either on, or instead of, maximal or near-maximal doses of OAD, mostly metformin and sulfonylureas; control subjects (n = 1,216) were patients with HbA1c <8% in the absence of insulin therapy. The IRS1 G972R polymorphism was typed by TaqMan allele discrimination. In all samples, individuals carrying the IRS1 R972 risk variant tended to be more frequent among case than control subjects, though reaching statistical significance only in one case. As no IRS1 G972R-by-study sample interaction was observed, data from the four samples were analyzed together; a significant association was observed (allelic odds ratio [OR] 1.30, 95% CI 1.03-1.63). When our present data were meta-analyzed with those obtained in a previous study, an overall R972 allelic OR of 1.37 (1.12-1.69) was observed. This study confirms in a large and ethnically homogeneous sample that IRS1 G972R polymorphism is associated with failure to OAD among patients with T2D.
本研究试图在来自意大利的大量2型糖尿病（T2D）白人患者样本中，重现先前报道的IRS1基因G972R多态性与口服抗糖尿病药物（OAD）治疗失败之间的关联。对来自四项独立研究的总共2409名患者进行了调查。病例组（n = 1193）为因糖尿病控制不佳（即糖化血红蛋白>8%）而加用胰岛素治疗，或用胰岛素替代最大剂量或接近最大剂量的OAD（主要是二甲双胍和磺脲类药物）的患者；对照组（n = 1216）为糖化血红蛋白<8%且未接受胰岛素治疗的患者。通过TaqMan等位基因鉴别法对IRS1基因G972R多态性进行分型。在所有样本中，携带IRS1基因R972风险变异的个体在病例组中往往比对照组更常见，不过仅在一个病例中达到统计学显著性。由于未观察到IRS1基因G972R与研究样本之间的相互作用，因此对四个样本的数据进行了合并分析；观察到显著关联（等位基因优势比[OR]为1.30，95%置信区间为1.03 - 1.63）。当将我们目前的数据与先前一项研究中获得的数据进行荟萃分析时，观察到R972等位基因的总体OR为1.37（1.12 - 1.69）。本研究在一个大型且种族同质的样本中证实，IRS1基因G972R多态性与T2D患者OAD治疗失败有关。
