Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1 genes in patients with early-onset Type 2 diabetes mellitus/MODY

Authors: Ng M.C.Y.; Cockburn B.N.; Lindner T.H.; Yeung V.T.F.; Chow C.-C.; So W.-Y.; Li J.K.Y.; Lo Y.M.D.; Lee Z.S.K.; Cockram C.S.; Critchley J.A.J.H.; Bell G.I.; Chan J.C.N.

Source: Diabetic Medicine, Volume 16, Number 11, November 1999 , pp. 956-963(8)

Publisher: Wiley-Blackwell

Abstract:

Aims To examine the prevalence of identified MODY-related genes in Chinese subjects with early onset Type 2 diabetes mellitus and a positive family history of diabetes and to look for possible associations between the gene mutations and the development of diabetes.

Methods Ninety-two unrelated Chinese subjects with diabetes diagnosed before the age of 40 years who had a positive family history of diabetes were screened for mutations in hepatocyte nuclear factors (HNF-1 and HNF-4) and glucokinase genes by direct sequencing. The family members of patients with mutations and 100 healthy controls were also examined.

Results Mutations in the HNF-1 and the glucokinase genes were found in 5% and 3% of the diabetic subjects, respectively but no mutations were found in the coding region of the HNF-4 gene. Three mutations found in the glucokinase gene were novel missense mutations (I110T, A119D and G385V). The mutations in the HNF-1 gene were also new and included four missense mutations (G20R, R203H, S432C, I618M) and one splice acceptor site mutation (IVS2nt-1GA). Patients with mutations in these genes were clinically heterogeneous with respect to phenotype and basal pancreatic beta cell function.

Conclusions Genetic factors such as mutations in the HNF-1 and glucokinase genes may be important in the development of diabetes in Chinese people, especially when the disease is of early onset.

Keywords: Chinese; early-onset Type 2 diabetes; glucokinase; HNF-1; HNF-4; maturity-onset diabetes of the young (MODY)

Language: English

Document Type: Research article

Publication date: 1999-11-01

• In this: publication
• By this: publisher
• In this Subject: Internal Medicine
• By this author: Ng M.C.Y. ;  Cockburn B.N. ;  Lindner T.H. ;  Yeung V.T.F. ;  Chow C.-C. ;  So W.-Y. ;  Li J.K.Y. ;  Lo Y.M.D. ;  Lee Z.S.K. ;  Cockram C.S. ;  Critchley J.A.J.H. ;  Bell G.I. ;  Chan J.C.N.

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