Identification of missense mutations in the hepatocyte nuclear factor-3 beta gene in Japanese subjects with late-onset Type II diabetes mellitus

Citation
Q. Zhu et al., Identification of missense mutations in the hepatocyte nuclear factor-3 beta gene in Japanese subjects with late-onset Type II diabetes mellitus, DIABETOLOG, 43(9), 2000, pp. 1197-1200
Citations number
9
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETOLOGIA
ISSN journal
0012-186X → ACNP
Volume
43
Issue
9
Year of publication
2000
Pages
1197 - 1200
Database
ISI
SICI code
0012-186X(200009)43:9<1197:IOMMIT>2.0.ZU;2-X
Abstract
Aims/hypothesis. Hepatocyte nuclear factor (HNF)3 beta, a transcription fac tor expressed in pancreatic beta cells, is an upstream regulator of HNF-1 a lpha/ MODY3, NNF-4 alpha/MODY1 and IPF1/MODY5 genes. Our previous screening of MODY subjects showed that mutations in the HNF-3 beta gene are not a co mmon cause of this form of diabetes in the Japanese, We tested the hypothes is that mutations in the HNF-3 beta gene cause late-onset Type II (non-insu lin-dependent) diabetes mellitus in this population. Methods. Genotyping of the polymorphic TCC repeat in the HNF-3 beta gene wa s done in 112 Japanese subjects with Type II diabetes (age at diagnosis > 3 5 and family history of Type II diabetes among their second-degree relative s) and 96 Japanese control subjects. Furthermore, we screened 57 Type II di abetic patients for mutations of the HNF-3 beta gene. Transactivation activ ity of variant HNF-3 beta was investigated by transfection assay. Results. The distribution of alleles of the TCC repeat was similar between diabetic and control groups. Mutation screening identified two missense mut ations, A86T and G114E, Neither mutation was observed in 225 control subjec ts. The transactivation activity of G114E-HNF-3 beta was similar to that of wild type-HNF3 beta. In contrast, the activity of A86T-HNF-3 beta was stat istically significantly reduced to 83-86% of that of wild type. Conclusions/Interpretation. The A86T mutation in the HNF-3 beta gene might be involved in the development of late-onset Type II diabetes in a small gr oup of Japanese people.