SLC22A1 rs12208357对2型糖尿病患者二甲双胍治疗反应的影响

IF 1.8 Q4 ENDOCRINOLOGY & METABOLISM
Journal of Diabetes and Metabolic Disorders Pub Date : 2024-08-28 eCollection Date: 2024-12-01 DOI:10.1007/s40200-024-01486-4
Reza Moazzami, Mohammad Yahya Vahidi Mehrjardi, Ali Miri
{"title":"SLC22A1 rs12208357对2型糖尿病患者二甲双胍治疗反应的影响","authors":"Reza Moazzami, Mohammad Yahya Vahidi Mehrjardi, Ali Miri","doi":"10.1007/s40200-024-01486-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>: Metformin, an oral hypoglycemic agent, is generally used as the first-line treatment in type 2 diabetes mellitus (T2DM) patients. The response to metformin varies between patients, and its mechanisms remain incompletely understood. Genetic variations in proteins involved in the pharmacodynamics and pharmacokinetics of metformin, like OCT1 transporter, are suspected to explain this difference. This study investigated the association of the response to metformin in T2DM patients with the presence of rs12208357 (R61C) variant in the <i>SLC22A1</i> gene.</p><p><strong>Materials and methods: </strong>We selected 100 patients who responded and 100 patients who did not respond to metformin monotherapy after 20 weeks according to their HbA1c level change. We investigated the effect of rs12208357 on the structure, function, and stability of OCT1 protein and its interaction with metformin by in silico tools. To determine the genotype of rs12208357 we used the ARMS-PCR technique.</p><p><strong>Results: </strong>The in silico study indicated that rs12208357 probably changes OCT1 stability, function, interaction site, and binding energy to metformin in the extracellular domain. ARMS-PCR also showed the frequency of T and C alleles were significantly different between responders and non-responders (<i>P-value</i> = 0.014), also there is a significant difference in CC and CT/TT genotype frequency between responders and non-responders (<i>P-value</i> = 0.023).</p><p><strong>Conclusion: </strong>Based on the in silico study and ARMS-PCR experiment results, the CC genotype has a better response to metformin therapy and the carrier of the T allele (CT and TT genotype) probably has complications in glycemic control by metformin.</p>","PeriodicalId":15635,"journal":{"name":"Journal of Diabetes and Metabolic Disorders","volume":"23 2","pages":"2183-2190"},"PeriodicalIF":1.8000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599672/pdf/","citationCount":"0","resultStr":"{\"title\":\"Impact of <i>SLC22A1</i> rs12208357 on therapeutic response to metformin in type 2 diabetes patients.\",\"authors\":\"Reza Moazzami, Mohammad Yahya Vahidi Mehrjardi, Ali Miri\",\"doi\":\"10.1007/s40200-024-01486-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>: Metformin, an oral hypoglycemic agent, is generally used as the first-line treatment in type 2 diabetes mellitus (T2DM) patients. The response to metformin varies between patients, and its mechanisms remain incompletely understood. Genetic variations in proteins involved in the pharmacodynamics and pharmacokinetics of metformin, like OCT1 transporter, are suspected to explain this difference. This study investigated the association of the response to metformin in T2DM patients with the presence of rs12208357 (R61C) variant in the <i>SLC22A1</i> gene.</p><p><strong>Materials and methods: </strong>We selected 100 patients who responded and 100 patients who did not respond to metformin monotherapy after 20 weeks according to their HbA1c level change. We investigated the effect of rs12208357 on the structure, function, and stability of OCT1 protein and its interaction with metformin by in silico tools. To determine the genotype of rs12208357 we used the ARMS-PCR technique.</p><p><strong>Results: </strong>The in silico study indicated that rs12208357 probably changes OCT1 stability, function, interaction site, and binding energy to metformin in the extracellular domain. ARMS-PCR also showed the frequency of T and C alleles were significantly different between responders and non-responders (<i>P-value</i> = 0.014), also there is a significant difference in CC and CT/TT genotype frequency between responders and non-responders (<i>P-value</i> = 0.023).</p><p><strong>Conclusion: </strong>Based on the in silico study and ARMS-PCR experiment results, the CC genotype has a better response to metformin therapy and the carrier of the T allele (CT and TT genotype) probably has complications in glycemic control by metformin.</p>\",\"PeriodicalId\":15635,\"journal\":{\"name\":\"Journal of Diabetes and Metabolic Disorders\",\"volume\":\"23 2\",\"pages\":\"2183-2190\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599672/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Diabetes and Metabolic Disorders\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/s40200-024-01486-4\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Diabetes and Metabolic Disorders","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40200-024-01486-4","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

二甲双胍是一种口服降糖药,一般作为2型糖尿病(T2DM)患者的一线治疗药物。对二甲双胍的反应因患者而异,其机制尚不完全清楚。与二甲双胍的药效学和药代动力学有关的蛋白质的遗传变异,如OCT1转运蛋白,被怀疑可以解释这种差异。本研究探讨了T2DM患者对二甲双胍的反应与SLC22A1基因中rs12208357 (R61C)变异的关系。材料和方法:我们根据HbA1c水平的变化,选择100例二甲双胍单药治疗20周后有反应的患者和100例无反应的患者。我们利用硅基工具研究了rs12208357对OCT1蛋白结构、功能和稳定性的影响及其与二甲双胍的相互作用。为了确定rs12208357的基因型,我们采用ARMS-PCR技术。结果:硅片研究表明rs12208357可能在胞外区域改变OCT1的稳定性、功能、相互作用位点和对二甲双胍的结合能。应答者与无应答者的T、C等位基因频率差异有统计学意义(p值= 0.014),CC和CT/TT基因型频率差异有统计学意义(p值= 0.023)。结论:基于计算机研究和ARMS-PCR实验结果,CC基因型对二甲双胍治疗有更好的应答,T等位基因携带者(CT和TT基因型)在二甲双胍降糖过程中可能存在并发症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of SLC22A1 rs12208357 on therapeutic response to metformin in type 2 diabetes patients.

Introduction: : Metformin, an oral hypoglycemic agent, is generally used as the first-line treatment in type 2 diabetes mellitus (T2DM) patients. The response to metformin varies between patients, and its mechanisms remain incompletely understood. Genetic variations in proteins involved in the pharmacodynamics and pharmacokinetics of metformin, like OCT1 transporter, are suspected to explain this difference. This study investigated the association of the response to metformin in T2DM patients with the presence of rs12208357 (R61C) variant in the SLC22A1 gene.

Materials and methods: We selected 100 patients who responded and 100 patients who did not respond to metformin monotherapy after 20 weeks according to their HbA1c level change. We investigated the effect of rs12208357 on the structure, function, and stability of OCT1 protein and its interaction with metformin by in silico tools. To determine the genotype of rs12208357 we used the ARMS-PCR technique.

Results: The in silico study indicated that rs12208357 probably changes OCT1 stability, function, interaction site, and binding energy to metformin in the extracellular domain. ARMS-PCR also showed the frequency of T and C alleles were significantly different between responders and non-responders (P-value = 0.014), also there is a significant difference in CC and CT/TT genotype frequency between responders and non-responders (P-value = 0.023).

Conclusion: Based on the in silico study and ARMS-PCR experiment results, the CC genotype has a better response to metformin therapy and the carrier of the T allele (CT and TT genotype) probably has complications in glycemic control by metformin.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Diabetes and Metabolic Disorders
Journal of Diabetes and Metabolic Disorders Medicine-Internal Medicine
CiteScore
4.80
自引率
3.60%
发文量
210
期刊介绍: Journal of Diabetes & Metabolic Disorders is a peer reviewed journal which publishes original clinical and translational articles and reviews in the field of endocrinology and provides a forum of debate of the highest quality on these issues. Topics of interest include, but are not limited to, diabetes, lipid disorders, metabolic disorders, osteoporosis, interdisciplinary practices in endocrinology, cardiovascular and metabolic risk, aging research, obesity, traditional medicine, pychosomatic research, behavioral medicine, ethics and evidence-based practices.As of Jan 2018 the journal is published by Springer as a hybrid journal with no article processing charges. All articles published before 2018 are available free of charge on springerlink.Unofficial 2017 2-year Impact Factor: 1.816.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信