강한 가족력을 갖는 한국인 조기발병 2형 당뇨병 환자에서 Hepatocyte Nuclear Factor-1α유전자의 다형성

Abstract

Background: Maturity-onset diabetes of the young (MODY) is a genetically heterogenous subtype of type 2 diabetes characterized by an early onset, usually before 25 years of age, autosomal dominant inheritance and a primary defect in insulin secretion. Mutation of the hepatocyte nuclear factor-1α (HNF-1α) gene is known to be a cause of MODY3. This study was carried out to reveal whether HNF-1α gene polymorphism is a common cause of early-onset type 2 diabetes and MODY in the Korean population.

Methods: Members of 12 pedigrees families with MODY and early-onset of type 2 diabetes were selected for the mutation detection. All of the families involved had at least two members with type 2 diabetes diagnosed before the age of 40 years, where the diabetes was inherited as an autosomal dominant trait, with at least 3 generations of diabetic subjects. Genomic DNA was extracted from whole-blood samples. The 10 exons and the promotor of the HNF-1α gene were sequenced.

Results: In codon 17 of exon 1, 2 of the 10 control subjects and 5 of the 12 patients had nucleotide replacement where the CTC nucleotide was replaced by the CTG (p=0.381). This is a silent mutation where both the CTC and CTG code have the same amino acid leucine. In codon 27 of exon 1, 5 patients had a silent mutation, where the codon ATC is replaced by CTC and the amino acid changes from isoleucine to leucine, but no mutation was found in the control group (p=0.040). In codon 459 of exon 7, 2 of the controls and 3 of the patient group had a silent mutation (CTG → TTG) that were both codon code leucine (p=1.000). Another missense mutation was observed in codon 487 of exon 7. Nucleotide AGC (serine) was replaced by AAC (asparagines). This mutation was observed in 5 control subjects and 10 patients (p=0.172).

Conclusion: This study did not reveal a new HNF-1α gene polymorphism. We conclude that the HNF-1α gene polymorphism does not play a major role in the early-onset of type 2 diabetes with a strong family history in Korea.