43 G > T polymorphism in the sucrase-isomaltase gene in the Chinese population prevents the glucose-lowering effect of acarbose.

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY Clinical biochemistry Pub Date : 2025-01-11 DOI:10.1016/j.clinbiochem.2025.110875

Junyao Huang, Yan Chen, Maolian Zhong, Yan Liu, Xing Wang, Wenqiang Xiong, Xiaodan Chen, Xiaoyi Yi, Yuting Liu, Hong Zhang

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Abstract

Background: Acarbose is an α-glucosidase inhibitor widely used clinically for its significant hypoglycemic effect, albeit with inter-individual variations in response. The sucrase-isomaltase (SI) enzyme is the primary target of acarbose. This study aims to investigate the impact of genetic polymorphisms in the SI gene on the pharmacodynamics of acarbose.

Methods: The Illumina sequencing platform and variation-related databases were employed to analyze probable gene polymorphism sites of SI. Based on the SI polymorphism sites, Chinese subjects (n = 66) were categorized into the wild-type homozygous group (Group A) and the heterozygous variant group (Group B, SI 43 G > T). The validated hexokinase method was utilized to determine glucose concentrations in participants' serum samples. The differences in blood glucose concentration reduction and pharmacodynamic parameters peak concentration (C_max) and area under the curve (AUC_0-2h) after administering the same dose of acarbose were analyzed between the two groups of subjects.

Results: Our results showed that the mean changes in glucose C_max, AUC_0-2h, maximum increase, and maximum decrease in Group B were each lower by 67.66 %, 63.05 %, 53.17 %, and 50 % compared to Group A (all p < 0.05).

Conclusions: These data suggested that genetic polymorphism of the SI gene can significantly influence the hypoglycemic efficacy of acarbose, and the polymorphism of SI is associated with individual differences in clinical treatment outcomes.

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43 G > 中国人群蔗糖-异麦芽糖酶基因的T多态性阻止了阿卡波糖的降血糖作用。

背景：阿卡波糖是一种α-葡萄糖苷酶抑制剂，因其显著的降糖作用而广泛应用于临床，但个体间的降糖反应存在差异。蔗糖-异麦芽糖酶（SI）酶是阿卡波糖的主要靶标。本研究旨在探讨SI基因遗传多态性对阿卡波糖药效学的影响。方法：利用Illumina测序平台和变异相关数据库对SI可能的基因多态性位点进行分析。根据SI多态性位点，将中国受试者（n = 66）分为野生型纯合子组（A组）和杂合子变异组（B组，SI 43 G > T）。采用已验证的己糖激酶法测定受试者血清样品中的葡萄糖浓度。分析两组受试者给予相同剂量阿卡波糖后血糖浓度降低及药效学参数峰浓度（Cmax）和曲线下面积（AUC0-2h）的差异。结果：我们的研究结果显示，与A组相比，B组血糖Cmax、AUC0-2h、最大增幅和最大降幅的平均变化分别降低67.66 %、63.05 %、53.17 %和50 % （p均为 ）。结论：这些数据提示SI基因的遗传多态性可显著影响阿卡波糖的降糖效果，SI基因的多态性与临床治疗结果的个体差异有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical biochemistry 医学-医学实验技术

CiteScore

5.10

自引率

0.00%

发文量

151

审稿时长

25 days

期刊介绍： Clinical Biochemistry publishes articles relating to clinical chemistry, molecular biology and genetics, therapeutic drug monitoring and toxicology, laboratory immunology and laboratory medicine in general, with the focus on analytical and clinical investigation of laboratory tests in humans used for diagnosis, prognosis, treatment and therapy, and monitoring of disease.