Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Division of Vascular Disease and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Pharmacogenomics J. 2024 Oct 7;24(6):31. doi: 10.1038/s41397-024-00352-z.
Our study investigated the impact of genetic variations on metformin glycemic response in a cohort from the Rotterdam Study, comprising 14,926 individuals followed for up to 27 years. Among 1285 metformin users of European ancestry, using linear mixed models, we analyzed the association of single nucleotide polymorphisms (SNPs) and a Polygenic Risk Score (PRS) with glycemic response, measured by changes in metformin dosage or HbA1c levels. While individual genetic variants showed no significant association, rs622342 on SLC2A1 correlated with increased glycemic response only in metformin monotherapy patients (β = -2.09, P-value < 0.001). The collective effect of variants, as represented by PRS, weakly correlated with changes in metformin dosage (β = 0.023, P-value = 0.027). Synergistic interaction was observed between rs7124355 and rs8192675. Our findings suggest that while higher PRS correlates with increased metformin dosage, its modest effect size limits clinical utility, emphasizing the need for future research in diverse populations to refine genetic risk models.
我们的研究调查了遗传变异对来自鹿特丹研究队列中二甲双胍血糖反应的影响，该队列包括 14926 名个体，随访时间长达 27 年。在 1285 名欧洲血统的二甲双胍使用者中，我们使用线性混合模型分析了单核苷酸多态性（SNP）和多基因风险评分（PRS）与血糖反应的关联，血糖反应通过二甲双胍剂量或 HbA1c 水平的变化来衡量。虽然个别遗传变异没有显示出显著的相关性，但 SLC2A1 上的 rs622342 仅在二甲双胍单药治疗患者中与血糖反应增加相关（β=−2.09，P 值<0.001）。PRS 代表的变异的综合效应与二甲双胍剂量的变化弱相关（β=0.023，P 值=0.027）。rs7124355 和 rs8192675 之间观察到协同交互作用。我们的研究结果表明，虽然较高的 PRS 与增加的二甲双胍剂量相关，但它的效应大小适中，限制了其临床实用性，强调需要在不同人群中进行进一步的研究，以完善遗传风险模型。
