Paired Box 4 (PAX4) variants increase the risk of type 2 diabetes (T2D) and influence response to the treatment with hypoglycemic agents (HAs) in certain Asian populations. However, the influence of PAX4 variants associated with T2D on response to the treatment with different HAs and their combinations is unclear. This study aims to investigate the effects of the PAX4 R192H (rs2233580) variant associated with T2D on the therapeutic efficacy of antidiabetic medications in Thai T2D after following up for 3 years. A total of 526 patients who were followed up at the Diabetic Clinic of Siriraj Hospital during 2016 - 20 were enrolled. The rs2233580 variant was genotyped by rhAmp analysis and assessed the associations between genotypes and glycemic control by treatment with different HAs combinations by Generalized Estimating Equations (GEE) analysis. The average age at diabetes diagnosis of the patients was 54.9±9.59 years and the average diabetes duration was 9.7±6.55 years. The patients who carried GA+AA genotypes and were treated with a combination of sulfonylurea (SU) , biguanide (Bi) , thiazolidinediones (TZD) , and insulin (Ins) had lower fasting plasma glucose (FPG) compared with that of the patients who carried GG genotype (p=0.02) but FPG levels were significantly higher in the patients who received SU monotherapy (p=0.04) . Lower HbA1c was observed in the patients who carried GA+AA genotype and SU-Bi-Ins treatment compared with that of the patients who carried wildtype (p=0.002) . A treatment of Bi-TZD-Ins yielded higher HbA1c levels in the patients who carried GA+AA genotype compared with that of the patients who carried GG genotype (p<0.001) . Therefore, different genotypes might distinctively impact therapeutic effect of HA combinations on FPG and HbA1c. Taken together, genotypes of the PAX4 R192H (rs2233580) variant associated with T2D influence the response to HA combinations, providing evidence of pharmacogenetics in diabetes treatment.
N.Teerawattanapong: None. W.Tangjittipokin: None. L.Srisawat: None. T.Narkdontri: None. P.Yenchitsomanus: None. N.Plengvidhya: None.