Molecular Scanning For HNF-1α Mutation In Jiangsu Population Of Familial Early-onset Diabetes Pedigrees

Objective To investigate the prevalence of mutations of hepatocyte nuclear factor (HNF)-1αgene in Jiangsu families with early-onset diabetes mellitus. Methods Forty pedigrees probands of early-onset type 2 diabetes were collected in Jiangsu, who were diagnosed as type 2 diabetes under 40 years old and, at least, another first relatives was diagnosed as type 2 diabetes under 45 years old. Another 48 non-diabetic subjects were enrolled as controls. By PCR, all the exons and exon / intron splice sites of MODY3 gene were amplified and PCR products were sequenced to identify the DNA variants. Results By screening MODY3 gene, 2 DNA variants were identified in coding region, including which we found one Leu459Leu samesense mutation and Ile27Leu mistake sense mutations in 40 probands. The Leu459Leu mutation frequency was 2.5%. It was co-segregated in the pedigree's members and was not found in normal control subjects. The Ile27Leu polymorphism allelic frequency in Chinese familial early-onset diabetes mellitus were A 0.65, C0.35 respectively, and in normal controls were A 0.71, C0.29, which had no difference between each other(P>0.05). Conclusion No enough evidence demonstrates that the variation in HNF-1αgene is the major cause of early-onset type 2 diabetes in Jiangsu population. A novel mutation of HNF-1αgene was found to possibly relate to diabetes, which mechanism needs to be proved by further study of protein function.