基因多态性对达格列净降糖作用的影响
The Impact of Genetic Polymorphisms on the Anti-Hyperglycemic Effect of Dapagliflozin.
作者信息
Wang Zi, Li Xiaoyu, Xu Qing, Yao Yao, Li Xiaoye, Yan Hongmei, Lv Qianzhou
机构信息
Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
出版信息
Diabetes Metab Syndr Obes. 2024 Jul 31;17:2881-2894. doi: 10.2147/DMSO.S464671. eCollection 2024.
BACKGROUND
The influence of genetic variants on the glucose-lowering effects of dapagliflozin remains unclear. This study aims to investigate the impact of polymorphisms in solute carrier family 5 member 2 (), uridine diphosphate glucuronosyltransferase 1A9 (), solute carrier family 2 member 2 () and member 4 () on the anti-hyperglycemic effect of dapagliflozin in patients with type-2 diabetes mellitus (T2DM).
METHODS
A total of 141 patients with T2DM were included in this prospective cohort study. Twenty-nine single nucleotide polymorphisms (SNPs) were selected and genotyped using the Sequenom MassArray platform or Sanger sequencing. Glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels were compared before and after the treatment with dapagliflozin.
RESULTS
Among the 29 SNPs selected, 27 were successfully analyzed. After three months of dapagliflozin treatment, FBG levels were significantly reduced (8.00 mmol/L (5.45-10.71) mmol/L vs 6.40 mmol/L (5.45-9.20) mmol/L, = 0.003) in patients with T2DM. However, there was no significant change in HbA1c levels (8.10% (6.88-10.00)% vs 8.10% (6.83-10.00)%, = 0.452). Analysis of covariance showed that patients with the minor allele homozygote or heterozygote of rs12471030 (CT/TT), rs12988520 (AC/CC) or rs2602381 (TC/CC) had higher FBG levels compared to those with the major allele homozygote ( = 0.014, = 0.024, and = 0.044, respectively). After adjusting for baseline FBG level, age, gender, body mass index, use of insulin and use of metformin, three SNPs-rs12471030, rs12988520 and rs2602381-were associated with the anti-hyperglycemic effect of dapagliflozin. However, using a stringent significance threshold ( < 0.002 with Bonferroni correction), none of these selected SNPs were significantly associated with FBG and HbA1c levels after dapagliflozin treatment.
CONCLUSION
After adjusting for confounding variables, polymorphisms in and genes were not associated with the anti-hyperglycemic effect of dapagliflozin in the Chinese population.
CLINICAL TRIAL REGISTRATION NUMBER
ChiCTR2200059645.
背景
基因变异对达格列净降糖效果的影响尚不清楚。本研究旨在探讨溶质载体家族5成员2（SLC5A2）、尿苷二磷酸葡萄糖醛酸基转移酶1A9（UGT1A9）、溶质载体家族2成员2（SLC2A2）和成员4（SLC2A4）基因多态性对2型糖尿病（T2DM）患者达格列净降糖效果的影响。
方法
本前瞻性队列研究共纳入141例T2DM患者。选择29个单核苷酸多态性（SNP），使用Sequenom MassArray平台或桑格测序法进行基因分型。比较达格列净治疗前后糖化血红蛋白（HbA1c）和空腹血糖（FBG）水平。
结果
在所选的29个SNP中，成功分析了27个。达格列净治疗3个月后，T2DM患者的FBG水平显著降低（8.00 mmol/L（5.45 - 10.71）mmol/L vs 6.40 mmol/L（5.45 - 9.20）mmol/L，P = 0.003）。然而，HbA1c水平无显著变化（8.10%（6.88 - 10.00）% vs 8.10%（6.83 - 10.00）%，P = 0.452）。协方差分析显示，rs12471030（CT/TT）、rs12988520（AC/CC）或rs2602381（TC/CC）的次要等位基因纯合子或杂合子患者的FBG水平高于主要等位基因纯合子患者（分别为P = 0.014、P = 0.024和P = 0.044）。在调整基线FBG水平、年龄、性别、体重指数、胰岛素使用情况和二甲双胍使用情况后，三个SNP（rs12471030、rs12988520和rs2602381）与达格列净的降糖效果相关。然而，使用严格的显著性阈值（经Bonferroni校正P < 0.002）时，这些所选SNP在达格列净治疗后均与FBG和HbA1c水平无显著关联。
结论
在调整混杂变量后，SLC5A2和UGT1A9基因多态性与中国人群中达格列净的降糖效果无关。
临床试验注册号
ChiCTR2200059645。
Zotero 插件