ObjectiveThe human Disabled-2 (Dab2) protein is an endocytic adaptor protein, which plays an essential role in endocytosis of transmembrane cargo, including low-density lipoprotein cholesterol (LDL-C). As a candidate gene for dyslipidemia, Dab2 is also involved in the development of type 2 diabetes mellitus(T2DM). The aim of this study was to investigate the effects of genetic variants of the Dab2 gene on the related risk of T2DM in the Uygur and Han populations of Xinjiang, China.MethodsA total of 2,157 age- and sex-matched individuals (528 T2DM patients and 1,629 controls) were included in this case-control study. Four high frequency SNPs (rs1050903,rs2255280,rs2855512andrs11959928) of the Dab2 gene were genotyped using an improved multiplex ligation detection reaction (iMLDR) genotyping assay, and the forecast value of the SNP for T2DM was assessed by statistical analysis of clinical data profiles and gene frequencies.ResultsWe found that in the Uygur population studied, for bothrs2255280andrs2855512, there were significant differences in the distribution of genotypes (AA/CA/CC), and the recessive model (CCvs.CA + AA) between T2DM patients and the controls (P< 0.05). After adjusting for confounders, the recessive model (CCvs.CA + AA) of bothrs2255280andrs2855512remained significantly associated with T2DM in this population (rs2255280: OR = 5.303, 95% CI [1.236 to −22.755],P= 0.025;rs2855512: OR = 4.892, 95% CI [1.136 to −21.013],P= 0.033). The genotypes (AA/CA/CC) and recessive models (CCvs.CA + AA) ofrs2855512andrs2255280were also associated with the plasma glucose and HbA1c levels (allP< 0.05) in this population. There were no significant differences in genotypes, all genetic models, or allele frequencies between the T2DM and control group in the Han population group (allP> 0.05).ConclusionsThe present study suggests that the variation of the Dab2 gene locirs2255280andrs2855512is related to the incidence of T2DM in the Uygur population, but not in the Han population. In this study, these variations in Dab2 were an independent predictor for T2DM in the Uygur population of Xinjiang, China.