rs622342多态性预测二甲双胍治疗的2型糖尿病患者胰岛素抵抗的改善：一项横断面研究。
rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study.
作者信息
Wu Kunrong, Li Xiaoli, Xu Yuedong, Zhang Xiaoqian, Guan Ziwan, Zhang Shufang, Li Yan
机构信息
Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Ji'nan 250014, China.
School of Pharmaceutical Sciences, Shandong First Medical University, Tai'an 271000, China.
出版信息
Int J Endocrinol. 2020 May 8;2020:2975898. doi: 10.1155/2020/2975898. eCollection 2020.
BACKGROUND
Metformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by ) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated () is a gene relating to the DNA repair and cell cycle control. The aim of this study was to evaluate if the genetic variants in rs622342 and rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment.
METHODS
This cross-sectional study included 111 patients with T2DM treated with metformin. Genotyping was performed by the dideoxy chain-termination method. The homeostatic indexes of IR (HOMA-IR) and beta-cell function (HOMA-BCF) were determined according to the homeostasis model assessment.
RESULTS
Fasting plasma glucose (FPG) levels, HbA levels, and HOMA-IR were significantly higher in patients with the rs622342 AA genotype than in those with C allele ( < 0.05). However, these significant differences were not observed between rs11212617 genotype groups. Further data analysis revealed that the association between the rs622342 polymorphism and HOMA-IR was gender related, and so was rs11212617 polymorphism and HOMA-BCF. HOMA-IR was significantly higher in males with rs622342 AA genotype than in those with C allele (=0.021), and HOMA-BCF value was significantly higher in females carrying rs11212617 CC genotype than in those with A allele (=0.038). The common logarithm (Lg10) of HOMA-BCF was positively correlated with the reciprocal of HbA ( = 0.629, < 0.001) and negatively associated with Lg10 FPG ( = -0.708, < 0.001).
CONCLUSIONS
The variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin. The association between the rs622342 polymorphism and HOMA-IR and the association between the rs11212617 polymorphism and HOMA-BCF were both gender related.
背景
二甲双胍是使用最广泛的口服抗糖尿病药物，能有效降低胰岛素抵抗（IR）。有机阳离子转运体1（由[具体基因名称未给出]编码）负责二甲双胍的转运，共济失调毛细血管扩张症突变基因（[具体基因名称未给出]）是一个与DNA修复和细胞周期控制相关的基因。本研究的目的是评估rs622342和rs11212617基因变异是否可作为2型糖尿病（T2DM）患者接受二甲双胍治疗时胰岛功能改善的有效预测指标。
方法
这项横断面研究纳入了111例接受二甲双胍治疗的T2DM患者。采用双脱氧链终止法进行基因分型。根据稳态模型评估法测定IR的稳态指标（HOMA-IR）和β细胞功能（HOMA-BCF）。
结果
rs622342基因AA基因型患者的空腹血糖（FPG）水平、糖化血红蛋白（HbA）水平和HOMA-IR显著高于携带C等位基因的患者（P<0.05）。然而，rs11212617基因各基因型组之间未观察到这些显著差异。进一步数据分析显示，rs622342基因多态性与HOMA-IR的关联与性别有关，rs11212617基因多态性与HOMA-BCF的关联也与性别有关。rs622342基因AA基因型男性的HOMA-IR显著高于携带C等位基因的男性（P=0.021），携带rs11212617基因CC基因型女性的HOMA-BCF值显著高于携带A等位基因的女性（P=0.038）。HOMA-BCF的常用对数（Lg10）与HbA的倒数呈正相关（r=0.629，P<0.oo1），与Lg10 FPG呈负相关（r=-0.708，P<0.001）。
结论
rs622342基因变异可能是接受二甲双胍治疗的T2DM患者胰岛素敏感性的预测指标。rs622342基因多态性与HOMA-IR的关联以及rs11212617基因多态性与HOMA-BCF的关联均与性别有关。
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