有机阳离子转运体基因多态性与 T2DM 个体中美比达药物反应和不耐受的关系：系统评价和荟萃分析。
Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis.
机构信息
Animal Laboratory, Shenzhen Center for Chronic Disease Control, Shenzhen, China.
Department of Epidemiology and Health Statistics, XiangYa School of Public Health, Central South University, Changsha, China.
出版信息
Front Public Health. 2023 Jul 21;11:1183879. doi: 10.3389/fpubh.2023.1183879. eCollection 2023.
BACKGROUND
Variants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM).
METHOD
A systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis.
RESULTS
A total of 30 related eligible studies about OCT genes (, and ) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in , and , respectively, were investigated. Meta-analysis showed that the rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = -0.45 [-0.73--0.18]; = 0.001). The GG genotype of the rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = -0.60 [-1.04-0.16], = 0.007; GG vs. AG: -0.45 [-0.67-0.20], < 0.001). No statistical association was found between the remaining variants and metformin response and intolerance.
CONCLUSION
rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes.
背景
有机阳离子转运体（OCT）基因的变异在二甲双胍药代动力学中起着至关重要的作用，对糖尿病的治疗至关重要。然而，研究OCT 基因多态性对二甲双胍反应的影响的报告结果不一致。本综述和荟萃分析旨在评估 2 型糖尿病（T2DM）个体中 OCT 基因多态性与二甲双胍反应和不耐受之间的关系。
方法
系统检索 PubMed、EMBASE、中国知网（CNKI）、万方数据和维普数据库，以确定截至 2022 年 11 月 10 日的潜在研究。使用 Q-Genie 工具评估纳入研究的质量。计算合并优势比（OR）或标准化均数差（SMD）和 95%置信区间（95%CI），以确定 OCT 基因多态性与血糖反应指标（如糖化血红蛋白水平（HbA1c%）或糖化血红蛋白水平变化（ΔHbA1c%）、空腹血糖水平（FPG）或空腹血糖水平变化（ΔFPG）、二甲双胍治疗的有效率和二甲双胍不耐受率之间的关系。对仅在一项研究中确定的变体和无法进行汇总分析的变体进行定性综述。
结果
共确定了 30 项关于 OCT 基因（和）和二甲双胍药物遗传学的相关研究，分别研究了和中的 14、3 和 6 个单核苷酸多态性（SNP）。荟萃分析显示，rs622342 多态性与 HbA1c 水平降低相关（AA 与 AC：SMD [95%CI] = -0.45 [-0.73--0.18]；= 0.001）。rs628031 多态性的 GG 基因型与 FPG 水平降低相关（GG 与 AA：SMD [95%CI] = -0.60 [-1.04-0.16]，= 0.007；GG 与 AG：-0.45 [-0.67-0.20]，<0.001）。其余变体与二甲双胍反应和不耐受之间无统计学关联。
结论
rs622342 和 rs628031 多态性可能与二甲双胍的血糖反应相关。这一证据可能为糖尿病的基因导向个体化医学提供新的见解。
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