SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study

Background. Metformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and...

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Main Authors: Kunrong Wu, Xiaoli Li, Yuedong Xu, Xiaoqian Zhang, Ziwan Guan, Shufang Zhang, Yan Li
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2020/2975898
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author Kunrong Wu
Xiaoli Li
Yuedong Xu
Xiaoqian Zhang
Ziwan Guan
Shufang Zhang
Yan Li
author_facet Kunrong Wu
Xiaoli Li
Yuedong Xu
Xiaoqian Zhang
Ziwan Guan
Shufang Zhang
Yan Li
author_sort Kunrong Wu
collection DOAJ
description Background. Metformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control. The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment. Methods. This cross-sectional study included 111 patients with T2DM treated with metformin. Genotyping was performed by the dideoxy chain-termination method. The homeostatic indexes of IR (HOMA-IR) and beta-cell function (HOMA-BCF) were determined according to the homeostasis model assessment. Results. Fasting plasma glucose (FPG) levels, HbA1c levels, and HOMA-IR were significantly higher in patients with the rs622342 AA genotype than in those with C allele (P<0.05). However, these significant differences were not observed between rs11212617 genotype groups. Further data analysis revealed that the association between the rs622342 polymorphism and HOMA-IR was gender related, and so was rs11212617 polymorphism and HOMA-BCF. HOMA-IR was significantly higher in males with rs622342 AA genotype than in those with C allele (P=0.021), and HOMA-BCF value was significantly higher in females carrying rs11212617 CC genotype than in those with A allele (P=0.038). The common logarithm (Lg10) of HOMA-BCF was positively correlated with the reciprocal of HbA1c (r = 0.629, P<0.001) and negatively associated with Lg10 FPG (r = −0.708, P<0.001). Conclusions. The variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin. The association between the rs622342 polymorphism and HOMA-IR and the association between the rs11212617 polymorphism and HOMA-BCF were both gender related.
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spelling doaj-art-fff527c1fd3648ecab2aaca666ca5ac42025-02-03T05:49:52ZengWileyInternational Journal of Endocrinology1687-83371687-83452020-01-01202010.1155/2020/29758982975898SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional StudyKunrong Wu0Xiaoli Li1Yuedong Xu2Xiaoqian Zhang3Ziwan Guan4Shufang Zhang5Yan Li6Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Ji’nan 250014, ChinaSchool of Pharmaceutical Sciences, Shandong First Medical University, Tai’an 271000, ChinaDepartment of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Ji’nan 250014, ChinaDepartment of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Ji’nan 250014, ChinaDepartment of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Ji’nan 250014, ChinaSchool of Pharmaceutical Sciences, Shandong First Medical University, Tai’an 271000, ChinaDepartment of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Ji’nan 250014, ChinaBackground. Metformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control. The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment. Methods. This cross-sectional study included 111 patients with T2DM treated with metformin. Genotyping was performed by the dideoxy chain-termination method. The homeostatic indexes of IR (HOMA-IR) and beta-cell function (HOMA-BCF) were determined according to the homeostasis model assessment. Results. Fasting plasma glucose (FPG) levels, HbA1c levels, and HOMA-IR were significantly higher in patients with the rs622342 AA genotype than in those with C allele (P<0.05). However, these significant differences were not observed between rs11212617 genotype groups. Further data analysis revealed that the association between the rs622342 polymorphism and HOMA-IR was gender related, and so was rs11212617 polymorphism and HOMA-BCF. HOMA-IR was significantly higher in males with rs622342 AA genotype than in those with C allele (P=0.021), and HOMA-BCF value was significantly higher in females carrying rs11212617 CC genotype than in those with A allele (P=0.038). The common logarithm (Lg10) of HOMA-BCF was positively correlated with the reciprocal of HbA1c (r = 0.629, P<0.001) and negatively associated with Lg10 FPG (r = −0.708, P<0.001). Conclusions. The variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin. The association between the rs622342 polymorphism and HOMA-IR and the association between the rs11212617 polymorphism and HOMA-BCF were both gender related.http://dx.doi.org/10.1155/2020/2975898
spellingShingle Kunrong Wu
Xiaoli Li
Yuedong Xu
Xiaoqian Zhang
Ziwan Guan
Shufang Zhang
Yan Li
SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study
International Journal of Endocrinology
title SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study
title_full SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study
title_fullStr SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study
title_full_unstemmed SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study
title_short SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study
title_sort slc22a1 rs622342 polymorphism predicts insulin resistance improvement in patients with type 2 diabetes mellitus treated with metformin a cross sectional study
url http://dx.doi.org/10.1155/2020/2975898
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