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二甲双胍单药治疗的墨西哥-梅斯蒂索2型糖尿病患者中(rs2252281和rs2289669)及(rs34834489和rs12943590)的多态性频率以及(rs72552763和rs622342)对糖化血红蛋白水平的影响

Frequency of Polymorphisms in (rs2252281 and rs2289669) and (rs34834489 and rs12943590) and the Influence of (rs72552763 and rs622342) on HbA1c Levels in Mexican-Mestizo Patients with DMT2 Treated with Metformin Monotherapy.

作者信息

Gómez-Hernández Milton Abraham, Ortega-Ayala Adiel, Rodríguez-Lima Oscar, Landa Abraham, Acosta-Altamirano Gustavo, Molina-Guarneros Juan A

机构信息

Programa de Doctorado en Ciencias Biomédicas, National Autonomous University of Mexico, Mexico City 04510, Mexico.

Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico.

出版信息

Int J Mol Sci. 2025 Sep 5;26(17):8652. doi: 10.3390/ijms26178652.

Abstract

Diabetes type 2 (DT2) entails significant health, economic, and productivity repercussions around the world. Poor glycaemic control, defined as an HbA1c >7.0%, has been associated with a number of complications. In spite of the large share of healthcare resources allocated to DT2 treatment, the proportion of controlled Mexican patients is among the lowest in the world (34.4%). Certain protein-encoding genetic polymorphisms involved in metformin transport may affect glycaemic control. We focused on determining the frequency of rs2289669, rs2252281, rs12943590, and rs34834489 polymorphisms in Mexican-Mestizo patients from the Tertiary Care Regional Hospital of Ixtapaluca, State of Mexico, Mexico, as well as assessing their possible association with therapeutic efficacy, as estimated through glycated haemoglobin. The individual polymorphism analysis did not reveal an association with glycaemic control; however, when combined with rs72552763 and rs622342, we found a significant positive correlation between HbA1c levels and metformin dose, which prevailed among patients carrying allelic variants of rs2289669 or rs12943590 who were also simultaneously carrying allelic variants of rs72552763 or rs622342. Patients carrying the reference allele of rs34834489 reported a significant positive correlation between HbA1c levels and metformin dose as well, regardless of their rs72552763 or rs622342 genotype. Thus, we identified alleles and allelic combinations of , , and polymorphisms posing a potential glycaemic control risk in Mexican-Mestizo patients.

摘要

2型糖尿病(DT2)在全球范围内对健康、经济和生产力都产生了重大影响。血糖控制不佳,定义为糖化血红蛋白(HbA1c)>7.0%,与多种并发症相关。尽管分配给DT2治疗的医疗资源占比很大,但墨西哥患者的血糖控制比例却是世界上最低的之一(34.4%)。某些参与二甲双胍转运的蛋白质编码基因多态性可能会影响血糖控制。我们重点研究了墨西哥伊斯特帕卢卡第三级区域医院的墨西哥梅斯蒂索患者中rs2289669、rs2252281、rs12943590和rs34834489多态性的频率,并通过糖化血红蛋白评估它们与治疗效果的可能关联。个体多态性分析未发现与血糖控制相关;然而,当与rs72552763和rs622342结合时,我们发现HbA1c水平与二甲双胍剂量之间存在显著正相关,这在同时携带rs2289669或rs12943590等位基因变体以及rs72552763或rs622342等位基因变体的患者中更为明显。携带rs34834489参考等位基因的患者,无论其rs72552763或rs622342基因型如何,其HbA1c水平与二甲双胍剂量之间也存在显著正相关。因此,我们确定了rs2289669、rs12943590和rs34834489多态性的等位基因和等位基因组合,这些组合在墨西哥梅斯蒂索患者中构成了潜在的血糖控制风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8207/12429666/d8971699da64/ijms-26-08652-g001.jpg

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