Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
Can J Diabetes. 2015 Feb;39(1):65-72. doi: 10.1016/j.jcjd.2014.05.003. Epub 2014 Oct 1.
The peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) gene could play a role in the onset of type 2 diabetes mellitus. The aim of this study was to explore the possible associations among polymorphisms Gly482Ser, Thr394Thr and Thr528Thr of the PGC-1alpha gene and the risk of type 2 diabetes in Kurdish-Iranians.
DNA specimens from all 173 type 2 diabetes subjects and 173 normoglycemic subjects were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostasis model assessment of insulin resistance and glycated hemoglobin levels were determined using the conventional methods. The data were analyzed using SPSS software.
The GA genotype of Gly482Ser was associated with a significant susceptibility for type 2 diabetes (odds ratio 5.23, p<0.000). Furthermore, the GA genotype of Thr528Thr had a higher risk for type 2 diabetes (odds ratio 2.37, p<0.002). Normoglycemic persons carrying the GA+AA genotypes of Gly482Ser variation had significantly lower high-density lipoprotein cholesterol in comparison with persons having GG genotype. In comparison with GG genotype carriers, normoglycemic subjects carrying the GA+AA genotypes of Thr394Thr variation had significantly higher fasting blood sugar, fasting serum insulin and homeostasis model assessment of insulin resistance. Normoglycemic subjects with the GA+AA genotypes of Thr528Thr variation had significantly higher levels of low-density lipoprotein cholesterol compared with subjects having the GG genotype. Type 2 diabetes subjects carrying the GA+AA genotypes of this polymorphism had significantly higher waist-hip ratio in comparison with the GG genotype carriers. We also found that haplotype 394-GG/482-GA/528-GG of PGC-1alpha was significantly associated with higher risk of type 2 diabetes.
Our findings revealed significant associations between PGC-1alpha Gly482Ser and Thr528Thr polymorphisms and type 2 diabetes in Kurdish-Iranians.
过氧化物酶体增殖物激活受体γ共激活因子 1α(PGC-1α)基因可能在 2 型糖尿病的发病中起作用。本研究旨在探讨 PGC-1α 基因 Gly482Ser、Thr394Thr 和 Thr528Thr 多态性与库尔德伊朗人 2 型糖尿病风险之间的可能关联。
通过聚合酶链反应-限制性片段长度多态性方法对所有 173 例 2 型糖尿病患者和 173 例血糖正常者的 DNA 标本进行基因分型。在每组中分析基因型和等位基因频率。使用常规方法测定血清脂质、空腹血糖、空腹血清胰岛素、胰岛素抵抗稳态模型评估和糖化血红蛋白水平。使用 SPSS 软件分析数据。
Gly482Ser 的 GA 基因型与 2 型糖尿病的显著易感性相关(优势比 5.23,p<0.000)。此外,Thr528Thr 的 GA 基因型患 2 型糖尿病的风险更高(优势比 2.37,p<0.002)。与 GG 基因型携带者相比,携带 Gly482Ser 变异 GA+AA 基因型的血糖正常者的高密度脂蛋白胆固醇明显降低。与 GG 基因型携带者相比,携带 Thr394Thr 变异 GA+AA 基因型的血糖正常者的空腹血糖、空腹血清胰岛素和胰岛素抵抗稳态模型评估均显著升高。与 GG 基因型携带者相比,携带 Thr528Thr 变异 GA+AA 基因型的血糖正常者的低密度脂蛋白胆固醇水平明显升高。携带该多态性 GA+AA 基因型的 2 型糖尿病患者的腰围-臀围比明显高于 GG 基因型携带者。我们还发现 PGC-1α 的 394-GG/482-GA/528-GG 单倍型与 2 型糖尿病的风险显著相关。
我们的研究结果表明,在库尔德伊朗人中,PGC-1α Gly482Ser 和 Thr528Thr 多态性与 2 型糖尿病之间存在显著关联。