Molecular Scanning On Hepatocyte Nuclear Factor-1 Alpha (HNF-1alpha) Gene In Chinese Familial Early-onset Type 2 Diabetes Mellitus/MODY Pedigrees And Sporadic Late-onset Type 2 Diabetes Mellitus

Objective: 1. To explore whether HNF-1 alpha gene mutations are the main genetic disorders which could cause the diseases in Chinese familial early-onset type 2 diabetes mellitus/MODY pedigrees. 2. After comparing the differences of genetic backgrounds between Chinese familial early-onset type 2 diabetes mellitus/MODY pedigrees and sporadic late-onset type 2 diabetes mellitus, to explore whether the mutation frequency of HNF-1 alpha gene was different from each other.Methods: Direct sequencing all the exons of HNF-1 alpha gene in 7 probands of Chinese early-onset type 2 diabetes pedigrees who were suspected to be MODY. Using denaturing high-performance liquid chromatograph (DHPLC) to filtrate the standard pictures for the mutations known after HNF-1 alpha gene sequencing. Using the same conditions of DHPLC to scan the same mutation in the rest members of the 7 pedigrees, 96 sporadic late-onset type 2 diabetes mellitus and 93 normal control subjects. Results: We found Leu17Leu, Leu459Leu and Gln486Gln same sense mutations and I27L,E105G,E73K, G184W, S487N and S574G mistakesense mutations in 7 probands. The I27L polymorphism allelic frequency in Chinese familial early-onset type 2 diabetes mellitus were A 0.70, C 0.30 respectively, and all of four CC genotype subjects were diabetes mellitus in 2 pedigrees, but the genotype frequency association analysis in all members of pedigrees had no difference between each other (0.25 G184W mutations in order to make sure whether they are new disease- associated gene mutations.