Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Clinical Pharmacy, Medical Affairs, Al-Baha Health Cluster, Al-Baha, Saudi Arabia.
Medicine (Baltimore). 2024 Nov 29;103(48):e40684. doi: 10.1097/MD.0000000000040684.
Type 2 diabetes mellitus (T2DM) is a chronic disease that affects millions of people worldwide. Metformin is the optimal initial therapy for patients with T2DM. Genetic factors play a vital role in metformin response, including variations in drug efficacy and potential side effects. To determine the effects of genetic variants of multidrug and toxin extrusion protein 2 (MATE2), ataxia telangiectasia mutated (ATM), and serine/threonine kinase 11 (STK11) genes on metformin response in a cohort of Saudi patients. This prospective observational study included 76 T2DM newly diagnosed Saudi patients treated with metformin monotherapy and 80 control individuals. Demographic data, lipid profiles, creatinine levels, and hemoglobin A1c (HbA1c) levels were collected before and after treatment. All participants were genotyped for 5 single-nucleotide polymorphisms (SNPs), including rs4621031, rs34399035, rs2301759, rs1800058, and rs11212617, using TaqMan R genotyping assays. This study included 156 subjects. The subjects' mean ± SD age was 50.4 ± 10.14 years. The difference in HbA1c levels in T2DM after treatment ranged from -1.20% to 8.8%, with a mean value of 0.927 ± 1.73%. In general, 73.7% of the patients with T2DM showed an adequate response to metformin (HbA1c < 7%). STK11 (rs2301759) significantly affects the response to metformin in T2DM patients. In the rs2301759 single-nucleotide polymorphisms, the prevalence of an adequate response to metformin was significantly higher among patients with C/C and T/C genotypes than among non-responders (P = .021). However, no statistically significant associations were observed for the other tested SNPs. Our study provides evidence of an association between STK11 (rs2301759) and response to metformin in Saudi patients with T2DM. The need for targeted studies on specific gene-drug associations is emphasized, and further studies with a larger population should be conducted.
2 型糖尿病（T2DM）是一种影响全球数百万人的慢性疾病。二甲双胍是 T2DM 患者的最佳初始治疗药物。遗传因素在二甲双胍反应中起着至关重要的作用，包括药物疗效和潜在副作用的变化。为了确定多药和毒素外排蛋白 2（MATE2）、共济失调毛细血管扩张突变（ATM）和丝氨酸/苏氨酸激酶 11（STK11）基因的遗传变异对沙特患者队列中二甲双胍反应的影响。这项前瞻性观察性研究包括 76 名新诊断为 T2DM 的沙特患者，他们接受二甲双胍单药治疗，80 名对照个体。治疗前后收集了人口统计学数据、血脂谱、肌酐水平和血红蛋白 A1c（HbA1c）水平。所有参与者均使用 TaqMan R 基因分型测定法对 5 个单核苷酸多态性（SNP）进行 rs4621031、rs34399035、rs2301759、rs1800058 和 rs11212617 的基因分型。这项研究包括 156 名受试者。受试者的平均年龄为 50.4±10.14 岁。T2DM 患者治疗后 HbA1c 水平的差异范围为-1.20%至 8.8%，平均值为 0.927±1.73%。一般来说，73.7%的 T2DM 患者对二甲双胍有足够的反应（HbA1c<7%）。STK11（rs2301759）显著影响 T2DM 患者对二甲双胍的反应。在 rs2301759 单核苷酸多态性中，C/C 和 T/C 基因型患者对二甲双胍的充分反应率明显高于无反应者（P=0.021）。然而，其他测试的 SNP 没有观察到统计学意义上的关联。我们的研究提供了证据表明，沙特 T2DM 患者的 STK11（rs2301759）与二甲双胍反应之间存在关联。强调需要针对特定基因-药物关联进行有针对性的研究，并应进行更大人群的进一步研究。
