PAX4 R192H is associated with younger onset of Type 2 diabetes in East Asians in Singapore.

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.