Genetic and clinical characteristics of maturity-onset diabetes of the young in Chinese patients
Authors:
- 15 December 2004
- journal article
- research article
- Published by Springer Nature in European Journal of Human Genetics
- Vol. 13 (4) , 422-427
Abstract
In Caucasians, maturity-onset diabetes of the young (MODY) is mostly caused by mutations in the hepatocyte nuclear factor (HNF)-1 (MODY3) and glucokinase (MODY2) genes. Most Japanese MODY patients, however, are not linked to known MODY genes. In this study, we examined the genetic and clinical characteristics of Chinese subjects with MODY. The study included 146 unrelated families fulfilling the minimum criteria for MODY: two consecutive generations of type II diabetes with at least one member diagnosed under the age of 25. We screened for mutations in the HNF-4 (MODY1), MODY2 and MODY3 genes by direct sequencing. Antibody to glutamic acid decarboxylase (GAD-Ab) was measured in subjects with MODY of unknown cause (MODYX). Insulin resistance index and other clinical data were compared in sex-, age- and duration-matched MODY3 and MODYX patients. In all, 13 families had MODY3 mutations and two had MODY2 mutations. No MODY1 mutation was found. Four of the 12 different MODY3 mutations were newly identified novel mutations (Q243E, A311D, P379R and P488fsdelC). In subjects with MODYX, 3% were GAD-Ab positive and 60% were overweight. Compared to MODY3 patients, MODYX patients had higher body mass index (PP=0.001) and triglyceride level (PP=0.001) and more hypertension (P<0.05), but no significant difference in the prevalence of diabetic complications. In conclusion, MODY3 and MODY2 account for only 9 and 1%, respectively, of Chinese MODY. A majority of Chinese MODY patients are due to defects in unknown genes and appear to be characterized by insulin resistance.Keywords
This publication has 24 references indexed in Scilit:
- Lifetime Risk for Diabetes Mellitus in the United StatesJAMA, 2003
- beta-cell genes and diabetes: molecular and clinical characterization of mutations in transcription factors.Diabetes, 2001
- The prevalence of diabetes, association with cardiovascular risk factors and implications of diagnostic criteria (ADA 1997 and WHO 1998) in a 1996 community‐based population study in Hong Kong ChineseDiabetic Medicine, 2000
- Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitusNature Genetics, 1999
- Mutation in hepatocyte nuclear factor–1β gene (TCF2) associated with MODYNature Genetics, 1997
- Organization and Partial Sequence of the Hepatocyte Nuclear Factor-4α/MODY1 Gene and Identification of a Missense Mutation, R127W, in a Japanese Family With MODYDiabetes, 1997
- Early-onset type-ll diabetes mellitus (MODY4) linked to IPF1Nature Genetics, 1997
- Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3)Nature, 1996
- Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1)Nature, 1996
- Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus.Proceedings of the National Academy of Sciences, 1992