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评价 MTNR1B rs10830963 基因变异在汉族 2 型糖尿病患者使用那格列奈治疗中的疗效影响。

Evaluation of the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating type 2 diabetes among Chinese Han patients.

机构信息

Department of Pharmacy, Affiliated Hospital of Jiangnan University , No.1000, Hefeng Road, Wuxi, 214000, China.

School of Pharmacy, Wannan Medical College, Wuhu, China.

出版信息

BMC Med Genomics. 2021 Jun 12;14(1):156. doi: 10.1186/s12920-021-01004-y.

DOI:10.1186/s12920-021-01004-y
PMID:34118937
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8196487/
Abstract

Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P < 0.05). Post 8-week of treatment, newly diagnosed T2DM patients showed a less reduction in fasting plasma glucose levels and less increase in the carriers of genotype CG + GG at rs10830963 when compared with the CC genotype (P < 0.05). MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.Trial registration Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.

摘要

MTNR1B 基因的遗传多态性与 2 型糖尿病(T2DM)有关;然而,尚无关于其对那格列奈治疗效果影响的证据。本前瞻性病例对照研究旨在探讨 MTNR1B rs10830963 基因变异对那格列奈治疗 T2DM 疗效的影响。我们使用高分辨率熔解曲线(HRM)法对未经治疗的 T2DM 患者(N=200)和健康对照者(N=200)进行基因分型。招募了新诊断的 CYP2C9*1 和 SLCO1B1 521TT 基因型的 T2DM 患者(n=60),并给予口服那格列奈(360mg/d)治疗 8 周。通过在治疗前和第 8 周收集静脉血样来评估疗效。MTNR1B rs10830963 的风险 G 等位基因频率在 T2DM 患者中高于健康受试者(P<0.05)。治疗 8 周后,与 CC 基因型相比,携带 rs10830963 基因型 CG+GG 的新诊断 T2DM 患者空腹血糖水平降低较少,增加较少(P<0.05)。MTNR1B rs10830963 多态性与那格列奈治疗 T2DM 患者的疗效相关。此外,CC 纯合子比 G 等位基因携带者的疗效更好。试验注册 中国临床试验注册中心 ChiCTR13003536,注册日期:2013 年 5 月 14 日。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd9a/8196487/4a53820d7f33/12920_2021_1004_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd9a/8196487/f4fdc5a60b81/12920_2021_1004_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd9a/8196487/4a53820d7f33/12920_2021_1004_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd9a/8196487/f4fdc5a60b81/12920_2021_1004_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd9a/8196487/4a53820d7f33/12920_2021_1004_Fig2_HTML.jpg

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