Mahmutovic Lejla, Bego Tamer, Sterner Maria, Gremsperger Gabriella, Ahlqvist Emma, Velija Asimi Zelija, Prnjavorac Besim, Hamad Nour, Causevic Adlija, Groop Leif, Semiz Sabina
Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnicka cesta 15, 71210 Ilidza, Sarajevo, Bosnia and Herzegovina, Phone: +387 61 950 675.
Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
Drug Metab Pers Ther. 2019 Mar 19;34(1):dmpt-2018-0031. doi: 10.1515/dmpt-2018-0031.
Background Previous studies reported conflicting results regarding association of insulin receptor substrate 1 (IRS1) gene variation with type 2 diabetes (T2D) and insulin resistance (IR) in different ethnic groups. We examined the association of rs7578326, rs2943641, and rs4675095 in the IRS1 gene with T2D and related traits in a population from Bosnia and Herzegovina, which is one of the European countries with the highest T2D prevalence of 12.5%. Methods Our study included 390 T2D patients and 252 control subjects. Biochemical parameters, including fasting glucose (FG), fasting insulin (FI), homeostasis model assessment insulin resistance index (HOMA-IR), and HbA1c were measured in all participants. Genotyping analysis was performed by Mass Array Sequenom iPlex platform. Results Our results demonstrated that rs7578326 and rs4675095 variants were associated with increased FG levels. The rs7578326 was also associated with higher FI, HOMA-IR (B = 0.08, 95% CI [0.01, 0.15], padd = 0.025; B = 0.079, 95% CI [0.006, 0.150], padd = 0.033, respectively) in T2D, and with HbA1c (B = 0.034, 95% CI [0.003, 0.065], pdom = 0.035) in non-drug-treated T2D. In contrast, rs2943641 C allele was associated with lower FG levels in control subjects (B = -0.17, 95% CI [-0.03, -0.002], padd = 0.030) and HbA1c (B = 0.03, 95% CI [0.002, 0.06], pdom = 0.040) in non-drug-treated T2D. Conclusions We report the association between common variants in IRS1 gene with insulin resistance, glucose, and HbA1c levels in Bosnia and Herzegovina's population.
背景 先前的研究报告了胰岛素受体底物1（IRS1）基因变异与不同种族的2型糖尿病（T2D）和胰岛素抵抗（IR）之间的关联结果相互矛盾。我们在波斯尼亚和黑塞哥维那的人群中研究了IRS1基因中的rs7578326、rs2943641和rs4675095与T2D及相关特征的关联，该国是欧洲T2D患病率最高（达12.5%）的国家之一。方法 我们的研究纳入了390例T2D患者和252例对照受试者。测量了所有参与者的生化参数，包括空腹血糖（FG）、空腹胰岛素（FI）、稳态模型评估胰岛素抵抗指数（HOMA-IR）和糖化血红蛋白（HbA1c）。通过Mass Array Sequenom iPlex平台进行基因分型分析。结果 我们的结果表明，rs7578326和rs4675095变异与FG水平升高有关。rs7578326还与T2D患者较高的FI、HOMA-IR（B = 0.08，95%置信区间[0.01，0.15]，padd = 0.025；B = 0.079，95%置信区间[0.006，0.150]，padd = 0.033）相关，并且与未接受药物治疗的T2D患者的HbA1c（B = 0.034，95%置信区间[0.003，0.065]，pdom = 0.035）相关。相比之下，rs2943641 C等位基因与对照受试者较低的FG水平（B = -0.17，95%置信区间[-0.03，-0.002]，padd = 0.030）以及未接受药物治疗的T2D患者的HbA1c（B = 0.03，95%置信区间[0.002，0.06]，pdom = 0.040）相关。结论 我们报告了波斯尼亚和黑塞哥维那人群中IRS1基因常见变异与胰岛素抵抗、血糖和HbA1c水平之间的关联。
