■遗传变异对达格列净降糖作用的影响尚不清楚。本研究旨在探讨溶质载体家族5成员2(SLC5A2)多态性的影响,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)对达格列净对2型糖尿病(T2DM)患者的降血糖作用。
■这项前瞻性队列研究共纳入了141例T2DM患者。使用SequenomMassArray平台或Sanger测序选择和基因分型二十九个单核苷酸多态性(SNP)。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。
■在所选的29个SNP中,27人分析成功。达格列净治疗三个月后,FBG水平显著降低(8.00mmol/L(5.45-10.71)mmol/Lvs6.40mmol/L(5.45-9.20)mmol/L,2型糖尿病患者p=0.003)。然而,HbA1c水平无显著变化(8.10%(6.88-10.00)%vs8.10%(6.83-10.00)%,p=0.452)。协方差分析表明,患者具有rs12471030(CT/TT)的次要等位基因纯合子或杂合子,与具有主要等位基因纯合子的那些相比,rs12988520(AC/CC)或rs2602381(TC/CC)具有更高的FBG水平(分别为p=0.014、p=0.024和p=0.044)。调整基线FBG水平后,年龄,性别,身体质量指数,使用胰岛素和二甲双胍,三个SNP-rs12471030,rs12988520和rs2602381-与达格列净的抗高血糖作用相关.然而,使用严格的显著性阈值(p<0.002,Bonferroni校正),这些选择的SNP均与达格列净治疗后的FBG和HbA1c水平无显著相关。
■调整混杂变量后,SLC5A2,UGT1A9,SLC2A2和SLC2A4基因的多态性与达格列净在中国人群中的抗高血糖作用无关。
■ChiCTR2200059645。
UNASSIGNED: 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 (SLC5A2), uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9), solute carrier family 2 member 2 (SLC2A2) and member 4 (SLC2A4) on the anti-hyperglycemic effect of dapagliflozin in patients with type-2 diabetes mellitus (T2DM).
UNASSIGNED: 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.
UNASSIGNED: 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, p = 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)%, p = 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 (p = 0.014, p = 0.024, and p = 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 (p < 0.002 with Bonferroni correction), none of these selected SNPs were significantly associated with FBG and HbA1c levels after dapagliflozin treatment.
UNASSIGNED: After adjusting for confounding variables, polymorphisms in SLC5A2, UGT1A9, SLC2A2 and SLC2A4 genes were not associated with the anti-hyperglycemic effect of dapagliflozin in the Chinese population.
UNASSIGNED: ChiCTR2200059645.