The effects of transcription factor 7-like 2 rs7903146 and paired box 4 rs2233580 variants associated with type 2 diabetes on the therapeutic efficacy of hypoglycemic agents
Nipaporn Teerawattanapong,
Lanraphat Srisawat,
Tassanee Narkdontri,
Pa-thai Yenchitsomanus,
Watip Tangjittipokin,
Nattachet Plengvidhya
Affiliations
Nipaporn Teerawattanapong
Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Lanraphat Srisawat
Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Tassanee Narkdontri
Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Pa-thai Yenchitsomanus
Siriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Watip Tangjittipokin
Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Corresponding author. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Nattachet Plengvidhya
Siriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Corresponding author. Division of Endocrinology and Metabolism, Department of Medicine Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Aim: This study aims to investigate the effects of the TCF7L2 rs7903146 and PAX4 rs2233580 (R192H) variants associated with T2D on the therapeutic efficacies of various HAs in patients with T2D after follow-up for 3 years. Methods: A total of 526 patients who were followed up at the Diabetic Clinic of Siriraj Hospital during 2016–2019 were enrolled. The variants TCF7L2 rs7903146 and PAX4 rs2233580 (R192H) were genotyped using the RNase H2 enzyme-based amplification (rhAmp) technique and the associations between genotypes and glycemic control after treatments with different combinations HA were evaluated using Generalized Estimating Equations (GEE) analysis. Results: Patients who carried TCF7L2 rs7903146C/T + T/T genotypes when they were treated with biguanide alone had significantly lower fasting plasma glucose (FPG) than those of the patients who carried the C/C genotype (p = 0.01). Patients who carried the PAX4 rs2233580 G/G genotype when they were treated with sulfonylurea alone had significantly lower FPG than those of the patients who carried G/A + A/A genotypes (p = 0.04). Conclusion: Genotypes of TCF7L2 rs7903146 and PAX4 rs2233580 (R192H) variants associated with T2D influence the therapeutic responses to biguanide and sulfonylurea. Different genotypes of these two variants might distinctively affect the therapeutic effects of HAs. This finding provides evidence of pharmacogenetics in the treatment of diabetes.
