OBJECTIVETo investigate the prevalence of mutations of hepatocyte nuclear factor (HNF)-1 alpha gene in Chinese families with early-onset and/or multiplex diabetes mellitus.

METHODSThe studied population consisted of 247 unrelated Chinese residents in Shanghai, including 93 healthy controls and 154 probands of early-onset and/or multiplex diabetes pedigrees. The ten exons, flanking introns and minimal promoter region of HNF-1 alpha gene were screened using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing.

RESULTSFourteen substitutions were identified in 154 probands. Three variants were not observed in 93 healthy controls. Two of them (nt-128T-->G IVS2 nt+21G-->A) were not reported previously and all co-segregated with diabetes. The genotype and allele frequencies of the other eleven variants in the diabetic patients were not significantly different from those in the healthy controls. There were no significant relationships between the eleven variants of HNF-1 alpha gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile).

CONCLUSIONHNF-1 alpha gene is not a major cause of early-onset or multiplex diabetes pedigrees in this Chinese population in Shanghai.