ISSN:
1432-0428
Schlagwort(e):
Keywords Keywords. HNF-3β
;
HNF-1α
;
mutation
;
genetics.
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract Aims/hypothesis. Hepatocyte nuclear factor (HNF)-3β, a transcription factor expressed in pancreatic beta cells, is an upstream regulator of HNF-1α/MODY3, HNF-4α/MODY1 and IPF1/MODY5 genes. Our previous screening of MODY subjects showed that mutations in the HNF-3 β gene are not a common cause of this form of diabetes in the Japanese. We tested the hypothesis that mutations in the HNF-3 β gene cause late-onset Type II (non-insulin-dependent) diabetes mellitus in this population. Methods. Genotyping of the polymorphic TCC repeat in the HNF-3 β gene was done in 112 Japanese subjects with Type II diabetes (age at diagnosis 〉 35 and family history of Type II diabetes among their second-degree relatives) and 96 Japanese control subjects. Furthermore, we screened 57 Type II diabetic patients for mutations of the HNF-3 β gene. Transactivation activity of variant HNF-3β 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 mutations, A86T and G114E. Neither mutation was observed in 225 control subjects. The transactivation activity of G114E-HNF-3β was similar to that of wild type-HNF-3β. In contrast, the activity of A86T-HNF-3β was statistically significantly reduced to 83–86 % of that of wild type. Conclusions/Interpretation. The A86T mutation in the HNF-3 β gene might be involved in the development of late-onset Type II diabetes in a small group of Japanese people. [Diabetologia (2000) 43: 1197–1200]
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s001250051512
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