한국인 인슐린 비의존형 당뇨병 및 이차성 당뇨병 환자에서 글루코키나제 유전자 변이

Abstract

Objectives: Mutations in the glucokinase (GCK) gene are considered a possible cause of maturity-onset diabetes of the young. The purpose of this study was to evaluate the contribution of this gene to the development of non insulin dependent diabetes mellitus (NIDDM), gestational diabetes mellitus (GDM) and post-renal transplantation diabetes mellitus (PTDM). Method: Identification of GCK mutation was attempted on 39 NIDDM patients, 2 GDM patients and 58 selected renal allograft recipients with PTDM and 45 normal controls. The exons in the GCK gene were examined by polymerase chain reaction (PCR), followed by analysis of single-stranded DNA conformational polymorphism (SSCP). The abnormal bands were also confirmed by DNA sequencing analysis. The exons of affected family members were also investigated for mutations of the GCK gene. Results: Two of the 58 PTDM patients (3.4%) were found to have CKK mutations. One had the mutation on exon 5 and the other on intron 7. One control subject had the mutation on intmn 9. The mutation of exon 5 was identified as a substitution of CCT (proline) for CTT (leucine) at codon 164, which has not ever reported before. The family members of the PFDM patient with mutation of exon 5 were analyzed by PCR followed by SSCP, and two of them revealed the same mutation. The abnormal band on the SSCP analysis of exon 7 was identified as the insertion of base C/T at the 39th nucleotide in intron 7. Two family members of this patients also had same band on SSCP. The one mutation of 45 normal controls was CT located at the 8th nucleotide in intron 9, which was a common polymorphism. Conclusion: We found GCK mutations in subjects with PTDM and we speculate that these mutations may be one of the contributing cause of PTDM.