突尼斯2型糖尿病患者中，根据有机阳离子转运体1基因多态性分析二甲双胍的疗效和耐受性
Metformin efficacy and tolerance according to genetic polymorphisms of organic cation transporter 1 in Tunisian patients with type 2 diabetes.
作者信息
Chaker Fatma, Kallel Ameni, Khessairi Nadia, Yazidi Meriem, Oueslati Ibtissem, Chatti Hiba Allah, Feki Moncef, Chihaoui Melika
机构信息
Department of Endocrinology, Rabta University Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Department of Biochemistry Rabta University Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
出版信息
Front Endocrinol (Lausanne). 2025 Jun 30;16:1536402. doi: 10.3389/fendo.2025.1536402. eCollection 2025.
PURPOSE
Metformin efficacy and tolerance vary at equivalent dose in type 2 diabetes. Inter-individual variability in the response to metformin with approximately 35% of patients failing to achieve initial glycemic control may be explained by genetic polymorphisms that affect the drug's pharmacokinetics and pharmacodynamics. Differences in the frequencies of pharmacogenomic risk alleles associated with metformin response may also account for interethnic variability in drug effects. The aim of this study was to assess the impact of M420del, R61c, and G401S polymorphisms in the SLC22A1 gene which encodes the organic cation transporter (OCT1) on metformin response and tolerance in a cohort of Tunisian patients with type 2 diabetes.
METHODS
This prospective study included 73 newly diagnosed type 2 diabetic patients. Clinical and biological assessments were conducted before and three months after initiation of metformin therapy. Patients were genotyped for the M420del, R61c, and G401S polymorphism of SLC22A1 using Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP) analysis. Metformin efficacy was defined as an HbA1c reduction of ≥ 1% and metformin- induced gastrointestinal adverse effects were recorded using a questionnaire.
RESULTS
Thirty-nine patients (53%) were classified as responders to metformin. The M420del, R61C and G401S variants were not significantly associated with metformin efficacy (p: 0.8, p: 0.77, and p: 0.49 respectively). Twenty-seven patients (37%) experienced gastrointestinal adverse effects following metformin initiation. The G401S polymorphism and the haplotype (NoDel) CA were significantly associated with gastrointestinal adverse effects.
CONCLUSION
In Tunisian type 2 diabetes, the M420del and R61C do not appear to be associated with metformin efficacy or the gastrointestinal intolerance. However, the G401S polymorphism may be implicated in the occurrence of metformine-induced gastrointestinal adverse effects.
目的
在2型糖尿病中，二甲双胍在等效剂量下的疗效和耐受性存在差异。约35%的患者未能实现初始血糖控制，对二甲双胍反应的个体间变异性可能由影响药物药代动力学和药效学的基因多态性来解释。与二甲双胍反应相关的药物基因组风险等位基因频率的差异也可能导致药物效应的种族间变异性。本研究的目的是评估编码有机阳离子转运体（OCT1）的SLC22A1基因中的M420del、R61c和G401S多态性对一组突尼斯2型糖尿病患者二甲双胍反应和耐受性的影响。
方法
这项前瞻性研究纳入了73例新诊断的2型糖尿病患者。在开始二甲双胍治疗前及治疗三个月后进行临床和生物学评估。采用聚合酶链反应（PCR），随后进行限制性片段长度多态性（RFLP）分析，对患者的SLC22A1基因的M420del、R61c和G401S多态性进行基因分型。二甲双胍疗效定义为糖化血红蛋白（HbA1c）降低≥1%，并使用问卷记录二甲双胍引起的胃肠道不良反应。
结果
39例患者（53%）被归类为二甲双胍反应者。M420del、R61C和G401S变异与二甲双胍疗效无显著相关性（p值分别为0.8、0.77和0.49）。27例患者（37%）在开始使用二甲双胍后出现胃肠道不良反应。G401S多态性和单倍型（NoDel）CA与胃肠道不良反应显著相关。
结论
在突尼斯2型糖尿病患者中，M420del和R61C似乎与二甲双胍疗效或胃肠道不耐受无关。然而，G401S多态性可能与二甲双胍引起的胃肠道不良反应的发生有关。
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