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二甲双胍药物遗传学:溶质载体家族22成员1(SLC22A1)、溶质载体家族22成员2(SLC22A2)和溶质载体家族22成员3(SLC22A3)基因多态性对血糖控制及糖化血红蛋白(HbA1c)水平的影响

Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels.

作者信息

Al-Eitan Laith N, Almomani Basima A, Nassar Ahmad M, Elsaqa Barakat Z, Saadeh Nesreen A

机构信息

Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan.

Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan.

出版信息

J Pers Med. 2019 Mar 25;9(1):17. doi: 10.3390/jpm9010017.

DOI:10.3390/jpm9010017
PMID:30934600
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6462993/
Abstract

Type 2 diabetes mellitus (T2DM) constitutes a major portion of Jordan's disease burden, and incidence rates are rising at a rapid rate. Due to variability in the drug's response between ethnic groups, it is imperative that the pharmacogenetics of metformin be investigated in the Jordanian population. The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the , , and genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus. Blood samples were collected from 212 Jordanian diabetics who fulfilled the inclusion criteria, which were then used in SNP genotyping and determination of HbA1c levels. The rs12194182 SNP in the gene was found to have a significant association ( < 0.05) with lower mean HbA1c levels, and this association more pronounced in patients with the CC genotype (i.e., -value was significant before correcting for multiple testing). Moreover, the multinomial logistic regression analysis showed that SNP genotypes within the , , and genes, body mass index (BMI) and age of diagnosis were significantly associated with glycemic control ( < 0.05). The results of this study can be used to predict response to metformin and other classes of T2DM drugs, making treatment more individualized and resulting in better clinical outcomes.

摘要

2型糖尿病(T2DM)构成了约旦疾病负担的主要部分,且发病率正在迅速上升。由于不同种族群体对药物的反应存在差异,因此有必要在约旦人群中研究二甲双胍的药物遗传学。本研究的目的是调查、和基因中的21个单核苷酸多态性(SNP)之间的关系及其对诊断为2型糖尿病的约旦患者二甲双胍药物遗传学的影响。从212名符合纳入标准的约旦糖尿病患者中采集血样,然后用于SNP基因分型和糖化血红蛋白(HbA1c)水平的测定。发现基因中的rs12194182 SNP与较低的平均HbA1c水平有显著关联(<0.05),并且这种关联在CC基因型患者中更为明显(即,在进行多重检验校正之前,-值具有显著性)。此外,多项逻辑回归分析表明,、和基因内的SNP基因型、体重指数(BMI)和诊断年龄与血糖控制显著相关(<0.05)。本研究结果可用于预测对二甲双胍和其他类T2DM药物的反应,使治疗更加个体化并产生更好的临床结果。

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SLAS Discov. 2019 Feb;24(2):89-110. doi: 10.1177/2472555218812821. Epub 2018 Dec 7.
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The SLC22 Transporter Family: A Paradigm for the Impact of Drug Transporters on Metabolic Pathways, Signaling, and Disease.SLC22 转运蛋白家族:药物转运蛋白对代谢途径、信号转导和疾病影响的范例。
Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:663-687. doi: 10.1146/annurev-pharmtox-010617-052713.
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The pharmacogenetics of metformin.二甲双胍的药物遗传学。
Diabetologia. 2017 Sep;60(9):1648-1655. doi: 10.1007/s00125-017-4335-y. Epub 2017 Aug 3.
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Arch Med Res. 2017 Feb;48(2):162-168. doi: 10.1016/j.arcmed.2017.03.010.
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Changes in metformin use in chronic kidney disease.慢性肾脏病中二甲双胍使用情况的变化
Clin Kidney J. 2017 Jun;10(3):301-304. doi: 10.1093/ckj/sfx017. Epub 2017 Mar 28.
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Association between the synonymous variant organic cation transporter 3 (OCT3)-1233G>A and the glycemic response following metformin therapy in patients with type 2 diabetes.2型糖尿病患者中同义变异有机阳离子转运体3(OCT3)-1233G>A与二甲双胍治疗后血糖反应之间的关联。
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