Department of Biochemistry, Kurukshetra University, Kurukshetra, 136119, India.
Mol Biol Rep. 2020 Dec;47(12):9489-9497. doi: 10.1007/s11033-020-05991-6. Epub 2020 Dec 2.
Insulin resistance may become the most powerful predictor of future development of type 2 diabetes mellitus (T2DM) and a therapeutic target for the treatment of the same. Both Resistin, an adipose derived peptide hormone and Urotensin II a potent vasoconstrictor, are reported to be involved in the development of insulin resistance and T2DM but the results remain contradictory. Therefore, investigations were carried out to study the association of T2DM and single nucleotide polymorphism (SNP) in Resistin (RETN) gene at rs3745367 (+ 299 G > A) and Urotensin II (UTS2) gene at rs228648 (+ 143 G > A) and rs2890565 (+ 3836 C > T) in a North Indian population. Method: The present case-control study, conducted from August 2017 to July 2020, involved 168 T2DM patients and 102 healthy controls. SNPs rs3745367, rs228648 and rs2890565 were amplified from genomic DNA in the studied samples by polymerase chain reaction (PCR) using specific primers. The amplified products were genotyped by restriction fragment length polymorphism (RFLP) using particular restriction endonucleases. Clinical parameters viz. glycosylated haemoglobin (HbA1c), fasting blood glucose (FBG), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (CHL) and fasting insulin were determined by enzymatic methods. Result and conclusion: A statistically significant association between T2DM and RETN gene at SNP rs3745367 (p = 0.001) and UTS2 gene at SNP rs2890565 (p = 0.001) was observed. In RETN gene SNP rs3745367, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were found to be higher in GA + AA combined genotype than in GG genotype for T2DM subjects. Regression analysis revealed that SNP rs2890565 and HOMA-IR were independently associated with the risk of development of T2DM when three SNPs were taken as independent variable adjusted for clinical variables. Among four haplotypes, A/T was found associated with increased risk of T2DM as determined for rs228648 and rs2890565 of UTS2 gene. It can be concluded from these results that polymorphism at rs3745367 of RETN gene and at rs2890565 of UTS2 gene are associated with risk of T2DM in North Indian population.
胰岛素抵抗可能成为 2 型糖尿病（T2DM）未来发展的最强预测因子，也是治疗该病的靶点。脂肪衍生肽激素抵抗素和强血管收缩素 Urotensin II 都被报道与胰岛素抵抗和 T2DM 的发展有关，但结果仍存在矛盾。因此，进行了研究以探讨在北印度人群中，T2DM 与抵抗素（RETN）基因单核苷酸多态性（SNP）rs3745367（+299 G> A）和 Urotensin II（UTS2）基因 rs228648（+143 G> A）和 rs2890565（+3836 C> T）之间的关联。方法：本病例对照研究于 2017 年 8 月至 2020 年 7 月进行，纳入了 168 例 T2DM 患者和 102 例健康对照。使用特定引物通过聚合酶链反应（PCR）从研究样本中的基因组 DNA 扩增 SNPs rs3745367、rs228648 和 rs2890565。使用特定的限制内切酶通过限制性片段长度多态性（RFLP）对扩增产物进行基因分型。通过酶法测定临床参数，如糖化血红蛋白（HbA1c）、空腹血糖（FBG）、高密度脂蛋白胆固醇（HDL-C）、甘油三酯（TG）、总胆固醇（CHL）和空腹胰岛素。结果与结论：T2DM 与 RETN 基因 SNP rs3745367（p=0.001）和 UTS2 基因 SNP rs2890565（p=0.001）之间存在统计学显著关联。在 RETN 基因 SNP rs3745367 中，与 GG 基因型相比，GA+AA 组合基因型的 T2DM 患者的胰岛素和胰岛素抵抗稳态模型评估（HOMA-IR）更高。回归分析显示，当将三个 SNP 作为独立变量并调整临床变量后，SNP rs2890565 和 HOMA-IR 与 T2DM 的发病风险独立相关。在四个单倍型中，发现 UTS2 基因的 rs228648 和 rs2890565 与 A/T 单倍型与 T2DM 风险增加相关。从这些结果可以得出结论，RETN 基因 rs3745367 多态性和 UTS2 基因 rs2890565 多态性与北印度人群的 T2DM 风险相关。
