The influence of SLC22A1 rs622342 and ABCC8 rs757110 genetic variants on the efficacy of metformin and glimepiride combination therapy in Egyptian patients with type 2 diabetes.

IF 2.4
Journal of Drug Assessment Pub Date : 2019-06-05 eCollection Date: 2019-01-01 DOI:10.1080/21556660.2019.1619571
Abdel-Hameed I M Ebid, Moataz Ehab, Ashraf Ismail, Sameh Soror, Mohamed Adel Mahmoud
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引用次数: 10

Abstract

Background: The incidence of Type 2 Diabetes Mellitus (T2DM) in Egypt is considered one of the highest in the world. Metformin and Sulfonylureas are usually prescribed together due to their efficacy and their relatively low cost. Organic cation transport 1, encoded by SLC22A1 gene, is the main transporter of metformin into hepatocytes, which is considered metformin site of action. Sulfonylureas enhance insulin release from pancreatic B-cells through binding to sulfonylurea receptor 1, encoded by ABCC8 gene. Single nucleotide polymorphisms in the SLC22A1 and ABCC8 genes might affect the response of each drug. Aims: To investigate the influence of SLC22A1 rs622342 (A>C) and ABCC8 rs757110 (A>C) genetic variants on the efficacy of metformin and glimepiride combination therapy in Egyptian T2DM patients. Methods: Observational cross-sectional study in which patients receiving metformin and glimepiride combination therapy for at least 6 months were included for genotyping and classified into either responders or non-responders, based on their HbA1C level. Results: A total of 127 patients were included and genotyped. They were divided into 93 responders (HbA1C<7%) and 34 non-responders (HbA1C≥7%). Minor allele frequencies for rs622342 and rs757110 were 0.189 and 0.271, respectively. Only SLC22A1 rs622342 variant was found to be associated with the response of combination therapy, in which AA alleles carriers were 2.7-times more responsive to metformin than C allele carriers (Recessive model, odds ratio = 2.718, p = 0.025, 95% CI = 1.112-6.385). Conclusion: Genotyping of rs622342 can be useful in predicting the response to metformin in combination therapy in Egyptian T2DM patients.

Abstract Image

SLC22A1 rs622342和ABCC8 rs757110基因变异对埃及2型糖尿病患者二甲双胍和格列美脲联合治疗疗效的影响
背景:埃及2型糖尿病(T2DM)的发病率被认为是世界上最高的国家之一。由于二甲双胍和磺脲类药物的疗效和相对较低的成本,通常一起开处方。SLC22A1基因编码的有机阳离子转运1是二甲双胍进入肝细胞的主要转运载体,被认为是二甲双胍的作用位点。磺酰脲类药物通过与ABCC8基因编码的磺酰脲受体1结合,促进胰腺b细胞胰岛素释放。SLC22A1和ABCC8基因的单核苷酸多态性可能会影响每种药物的疗效。目的:探讨SLC22A1 rs622342 (A>C)和ABCC8 rs757110 (A>C)基因变异对埃及T2DM患者二甲双胍与格列美脲联合治疗疗效的影响。方法:观察性横断面研究,纳入接受二甲双胍和格列美脲联合治疗至少6个月的患者进行基因分型,并根据其HbA1C水平分为反应者和无反应者。结果:共纳入127例患者并进行基因分型。他们被分为93例应答者(HbA1CSLC22A1 rs622342变异与联合治疗的应答相关,其中AA等位基因携带者对二甲双胍的应答是C等位基因携带者的2.7倍(隐性模型,优势比= 2.718,p = 0.025, 95% CI = 1.112-6.385)。结论:rs622342基因分型可用于预测埃及T2DM患者对二甲双胍联合治疗的反应。
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来源期刊
Journal of Drug Assessment
Journal of Drug Assessment PHARMACOLOGY & PHARMACY-
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