Dataset Information

KCNQ1 rs2237895 polymorphism is associated with the therapeutic response to sulfonylureas in Iranian type 2 diabetes mellitus patients.

ABSTRACT:

Background and aims

Sulfonylureas are the most secondary prescribed oral anti-diabetic drug. Understanding its genetic role in pharmacodynamics can elucidate a considerable knowledge about personalized treatment in type 2 diabetes patients. This study aimed to assess the impact of KCNQ1 variants on sulfonylureas response among type 2 diabetes Iranian patients.

Methods and results

100 patients were recruited who were under sulfonylureas therapy for six months. 50 responder and 50 non-responder patients were selected. KCNQ1 variants were determined by the RFLP method, and their role in treatment response was assessed retrospectively. Patients with rs2237895 CC and AC genotypes demonstrated a significant decrement in FBS and HbA1c after treatment over patients with AA genotypes (All P < 0.001). Compared to the A allele, the odds ratio for treatment success between carriers with rs2237895 C allele was 4.22-fold (P < 0.001). Patients with rs2237892 CT heterozygous genotype exhibit a higher reduction rate in HbA1c and FBS than CC homozygotes (P=0.064 and P=0.079, respectively). The rs2237892 T allele carriers showed an odds ratio equals to 2.83-fold over C allele carriers in the responder group compared to the non-responder group (p=0.081).

Conclusion

Findings suggest that the KCNQ1 rs2237895 polymorphism is associated with the sulfonylureas response on Iranian type 2 diabetes patients.

SUBMITTER: Shakerian S

PROVIDER: S-EPMC9167421 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

<i>KCNQ1</i> rs2237895 polymorphism is associated with the therapeutic response to sulfonylureas in Iranian type 2 diabetes mellitus patients.

Shakerian Siavash S Rashidi Homeira H Birgani Maryam Tahmasebi MT Saberi Alihossein A

Journal of diabetes and metabolic disorders 20220111 1

<h4>Background and aims</h4>Sulfonylureas are the most secondary prescribed oral anti-diabetic drug. Understanding its genetic role in pharmacodynamics can elucidate a considerable knowledge about personalized treatment in type 2 diabetes patients. This study aimed to assess the impact of <i>KCNQ1</i> variants on sulfonylureas response among type 2 diabetes Iranian patients.<h4>Methods and results</h4>100 patients were recruited who were under sulfonylureas therapy for six months. 50 responder a ...[more]

PMID: 35673481

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Project description:KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gliclazide MR) treatment in Chinese patients newly diagnosed with T2DM. A total of 100 newly diagnosed T2DM patients without a history of any anti-diabetic medications were treated with gliclazide MR for 16 weeks, but 91 patients completed the entire study. The anthropometric parameters were determined at baseline and at the final visit, while clinical laboratory tests were performed at baseline and on weeks 2, 4, 6, 12, 16. Two SNPs, rs2237892 and rs2237895, in the region of the KCNQ1 gene were genotyped in all the participants. All calculations and statistical analyses were conducted using SPSS. The rs2237892 TT homozygotes exhibited significantly higher 2-h glucose levels at baseline (P<0.05) and a lower cumulative attainment rate of the target 2-h glucose level (Plog-rank=0.020) than the C allele carriers. Patients with greater numbers of rs2237892 T alleles exhibited larger augmentations (Δ) in the 2-h glucose levels (P=0.027); and patients with the rs2237892 TT genotype exhibited a higher Δ homeostasis model assessment of β-cell function (HOMA-β) than CC and CT genotype carriers (P=0.021 and P=0.043, respectively). Moreover, the rs2237895 C allele was associated with a greater decrement in Δ glycated hemoglobin (HbA1c) (P=0.024); and patients with the CC genotype exhibited greater variance than those with the AA and AC genotypes (P=0.005 and 0.021, respectively). Compared with the C allele, the odds ratio for treatment success among carriers of the rs2237892 T allele was 2.533 (P=0.007); and the rs2237895 C allele was associated with a 2.360-fold decrease in HbA1c compared with the A allele (P=0.009). KCNQ1 polymorphisms are associated with gliclazide MR efficacy in Chinese patients with type 2 diabetes.