Aims: Young-onset T2D (YT2D) is associated with a more fulminant course and greater propensity for diabetic complications. The association of PAX4 R192H (rs2233580) variation with YT2D was inconsistent partly because of its Asian-specificity and under-representation of Asians in international consortiums. Interestingly, in our preliminary YT2D (mean = 25 years old) cohort, the prevalence of PAX4 R192H variant was remarkably higher (21.4%) than the general population. Therefore, we sought to determine whether PAX4 R192H is associated with younger onset of T2D in our East Asian (Chinese) population.
Methods: Genotyping of PAX4 R192H was carried out using Illumina OmniExpress BeadChips as part of a genome-wide association study. Data analysis was performed using SPSS Ver. 22.
Results: PAX4 R192H genotype was associated with younger onset age (CC: 47.1, CT: 46.0, TT: 42.6) after adjusting for gender, F = 5.402, p = 0.005. Independently, onset of diabetes was younger among males by 2.52 years, 95% CI [-3.45, -1.59], p < 0.0001. HOMA-IR and HOMA-%B were not significantly different across genotypes for a subset (n = 1045) of the cohort.
Conclusions: Minor allele (T) of PAX4 R192H is associated with younger onset diabetes among Chinese in Singapore. Determining this genotype is important for identifying at-risk individuals for earlier onset diabetes and diabetic complications.
Keywords: Beta-cell dysfunction; MODY; PAX4; Type 2 diabetes; Young-onset.
Copyright © 2018. Published by Elsevier Inc.