Mutation in hepatocyte nuclear factor-1alpha is not a common cause of MODY and early-onset type 2 diabetes in Korea.

Maturity-onset diabetes of the young (MODY)-3 with a mutation in hepatocyte nuclear factor (HNF)-1alpha has been identified in most races, but the prevalence of Korean MODY and early-onset type 2 diabetes with a mutation in this gene is unknown. To determine the prevalence of MODY and early-onset type 2 diabetes with the mutation of HNF-1alpha gene in Korea, we analyzed this gene in 69 Korean early-onset type 2 diabetics and in 35 healthy persons using the single-strand conformation polymorphism (SSCP) technique and direct sequencing. We identified one mutation in exon 4 (C900A) in only one of the 69 Korean subjects with early-onset type 2 diabetes; this mutation was silent and did not change the amino acid (Pro300). Additionally, we identified four polymorphisms: S487N, AAC-->AGC, intron 2 (nt -23), intron 7: (nt +7) and intron 9 (nt -24). However, there was no significant difference in frequencies of the four polymorphisms between the type 2 diabetes and control groups. Among type 2 diabetics, codon 487 variant showed no relationship to age at onset, body mass index, fasting blood glucose, HbA1c, lipid profile, basal C-peptide and 2 hour C-peptide. We concluded that this genetic mutation in HNF-1alpha gene may not be a common contributor to MODY and early-onset type 2 diabetes susceptibility in Korea.