ISSN:
1432-0428
Schlagwort(e):
Keywords Maturity-onset diabetes of the young
;
MODY
;
transcription factor
;
nuclear receptor
;
HNF-4γ
;
diabetes mellitus
;
insulin
;
genetics
;
mutation.
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract Aims/hypothesis. Mutations in the transcription factor hepatocyte nuclear factor (HNF)-4α are the cause of one form of maturity-onset diabetes of the young, MODY1. The HNF-4γ is structurally related to HNF-4α and is expressed together with HNF-4α in pancreatic islets. We therefore tested the hypothesis that genetic variation in the HNF-4γ gene (HNF4G) is associated with MODY in Japanese subjects. Methods. We screened the protein coding region of HNF4G (exons 3–11) for mutations in 57 unrelated Japanese subjects with MODY by amplifying each exon and adjacent intron region using the polymerase chain reaction (PCR) and specific primers and then directly sequencing the PCR products. The frequency of each variant was compared between patients with MODY and a group of non-diabetic subjects. Results. We found ten sequence variants, two of these were located in exons: exon 6, a silent substitution in codon 144, c.432A/G and exon 7, a G-to-A substitution in codon 190 (c.570G/A) resulting in a conservative Met-to-Ile substitution (M/I190) in the putative ligand-binding region of HNF-4γ protein. The remaining eight variants were located in introns. There was no significant difference in the frequency of these polymorphisms between subjects with MODY and non-diabetic control subjects. Conclusion/interpretation. Genetic variation in the coding region of HNF4G is unlikely to be a major cause of MODY in Japanese people. [Diabetologia (2000) 43: 1064–1069]
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s001250051491
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