Genetic variation in the hepatocyte nuclear factor-3β gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians

Amar Abderrahmani, Jean Claude Chèvre, Shuichi Otabe, Mohamed Chikri, El Habib Hani, Martine Vaxillaire, Yoshinori Hinokio, Yukio Horikawa, Graeme I. Bell, Philippe Froguel

Research output: Contribution to journalArticle

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Abstract

Mutations in genes encoding hepatocyte nuclear factor (HNF) are responsible for three of the five subtypes of maturity-onset diabetes of the young (MODY). This observation and molecular studies indicate that the HNF network is required for normal function of pancreatic β-cells. This suggests that transcription factors involved in this complex network are candidates for genetic defects in MODY. Because the HNF-3β gene is implicated in this network, we screened it for mutations in 21 probands of French ancestry with clinical diagnosis of MODY and early-onset type 2 diabetes. All of the five known MODY genes, HNF-4α, glucokinase, HNF-1α, HNF-1β, and IPF1, were previously excluded as being the cause of diabetes in these families. By direct sequencing, we identified two transitions, an A-to-G at position -213 and a C-to-T at position -63 in the promoter and exon 1, respectively, of the HNF-3β gene. A G-to-C transversion at position +32 in the intron I and three transitions, C-to-T at position 291, A-to-G at position 837, and G-to-A at position 1188 in the exon 3, resulting in noncoding mutations Ala97Ala, Gly279Gly, and Gln396Gln, respectively, were also identified. The allele frequencies were not significantly different between a control group and MODY probands. Familial segregation studies and linkage analysis showed that genetic variation in the HNF-3β gene is unlikely to be the cause of early- onset type 2 diabetes in these Caucasian families.

Original languageEnglish
Pages (from-to)306-308
Number of pages3
JournalDiabetes
Volume49
Issue number2
Publication statusPublished - 1 Feb 2000
Externally publishedYes

Fingerprint

Hepatocyte Nuclear Factors
Hepatocyte Nuclear Factor 1
Genes
Type 2 Diabetes Mellitus
Mutation
Exons
Hepatocyte Nuclear Factor 4
Glucokinase
Gene Frequency
Introns
Transcription Factors
Mason-Type Diabetes
Control Groups

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Abderrahmani, A., Chèvre, J. C., Otabe, S., Chikri, M., Hani, E. H., Vaxillaire, M., ... Froguel, P. (2000). Genetic variation in the hepatocyte nuclear factor-3β gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians. Diabetes, 49(2), 306-308.

Genetic variation in the hepatocyte nuclear factor-3β gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians. / Abderrahmani, Amar; Chèvre, Jean Claude; Otabe, Shuichi; Chikri, Mohamed; Hani, El Habib; Vaxillaire, Martine; Hinokio, Yoshinori; Horikawa, Yukio; Bell, Graeme I.; Froguel, Philippe.

In: Diabetes, Vol. 49, No. 2, 01.02.2000, p. 306-308.

Research output: Contribution to journalArticle

Abderrahmani, A, Chèvre, JC, Otabe, S, Chikri, M, Hani, EH, Vaxillaire, M, Hinokio, Y, Horikawa, Y, Bell, GI & Froguel, P 2000, 'Genetic variation in the hepatocyte nuclear factor-3β gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians', Diabetes, vol. 49, no. 2, pp. 306-308.
Abderrahmani, Amar ; Chèvre, Jean Claude ; Otabe, Shuichi ; Chikri, Mohamed ; Hani, El Habib ; Vaxillaire, Martine ; Hinokio, Yoshinori ; Horikawa, Yukio ; Bell, Graeme I. ; Froguel, Philippe. / Genetic variation in the hepatocyte nuclear factor-3β gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians. In: Diabetes. 2000 ; Vol. 49, No. 2. pp. 306-308.
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