These results strongly suggest that the high frequency of the T130I polymorphism and its biological relationship with dysfunction in lipid metabolism in Mexican indigenous groups is a risk factor for the developing of T2D in Mexicans.
Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes.
Previous studies in the Mexican population have shown a high frequency of the Thr130Ile polymorphism and have suggested its important role in the pathogenesis of early-onset type 2 diabetes.
Our data are consistent with T130I as a low-frequency variant influencing type 2 diabetes risk, but are not conclusive when judged against stringent standards for genome-wide significance.
In conclusion, The Thr130Ile and the Val255Met polymorphisms decrease the transcriptional activity of HNF4A, and the Thr130Ile polymorphism associates with T2D, whereas the Val255Met variant associates with a decrease in fasting serum C-peptide.