Association between the synonymous variant organic cation transporter ۳ (OCT۳)-۱۲۳۳G>A and the glycemic response following metformin therapy in patients with type ۲ diabetes
Publish place: Iranian Journal of Basic Medical Sciences، Vol: 20، Issue: 3
Publish Year: 1396
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:
JR_IJBMS-20-3_003
تاریخ نمایه سازی: 28 مهر 1400
Abstract:
Objective(s): Organic cation transporter ۳ (OCT۳) as a high-capacity transporter contribute to the metabolism of metformin. The present study was conducted to determine the genotype frequencies of the variant OCT۳-۱۲۳۳G>A (rs۲۲۹۲۳۳۴) in patients with newly diagnosed type ۲ diabetes (T۲D) and its relationship with response to metformin. Materials and Methods: This study included ۱۵۰ patients with T۲D who were classified into two groups following three months of metformin therapy: responders (by more than ۱% reduction in HbA۱c from baseline) and nonresponders (less than ۱% reduction in HbA۱c from baseline). PCR-based restriction fragment length polymorphism (RFLP) served to genotype OCT۳-۵۶۴G>A variant. Results: The parameters such as HbA۱c (P<۰.۰۰۱) and BMI (P<۰.۰۰۱) in both patients with GA + AA genotype and GG genotype decreased significantly following ۳ months of metformin therapy compared with baseline. The mean reduction in HbA۱c levels following ۳ months was higher in patients with the A allele (۰.۷۷% reduction from baseline) than in those with the homozygous G allele (۰.۵۴% reduction from baseline). Also, in GA + AA genotypes compared with GG genotypes, the mean reduction in HbA۱c values from baseline was ۰.۳۴% for responders and ۰.۱۴% for non-responders. Conclusion: Considering the roles of genetic variations in the function of metformin transporters, the effect of variations such as ۱۲۳۳G>A in the OCT۳, which is a high-capacity transporter widely expressed in various tissues cannot be ignored. Comparing the allele frequencies of OCT۳-۱۲۳۳G>A variant in our study and different ethnic populations confirm that the variant is a highly polymorphic variant.
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Authors
Seyyedeh Raheleh Hosseyni-Talei
Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Abdolkarim Mahrooz
Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Mohammad Bagher Hashemi-Soteh
Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Maryam Ghaffari-Cherati
Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Ahad Alizadeh
Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
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