Variants in the hepatocyte nuclear factor-1alpha and -4alpha genes in Finnish and Chinese subjects with late-onset type 2 diabetes.

Abstract

OBJECTIVE:

To determine the role of the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in the etiology of late-onset type 2 diabetes in Finnish and Chinese subjects.

RESEARCH DESIGN AND METHODS:

The whole coding regions of the genes encoding for HNF-1alpha and HNF-4alpha, including approximately 800 bp of the HNF-1alpha promoter, were investigated in 40 Finnish subjects (fasting C-peptide 50-570 pmol/l) and 47 Chinese subjects with type 2 diabetes by single-strand conformation polymorphism (SSCP) analysis. Frequencies of the variants of these genes were analyzed by restriction fragment-length polymorphism analysis in additional samples of 100 Finnish diabetic patients and 82 Finnish control subjects and in 58 Chinese diabetic patients and 51 Chinese control subjects.

RESULTS:

No previously reported gene defects were detected, but one novel functionally silent GCC-->GCG variant (nucleotide 73, exon 10) was observed in the HNF-4alpha gene in a Chinese diabetic patient. Interestingly, the Ala98Val substitution of the HNF-1alpha gene occurred at a significantly higher frequency in 140 Finnish diabetic patients compared with 82 control subjects (P = 0.014). The Ala98Val variant was not, however, associated with abnormalities in insulin secretion evaluated by oral and intravenous glucose tolerance tests in subjects with normal (n = 295) or impaired (n = 38) glucose tolerance.

CONCLUSIONS:

Variants in the HNF-1alpha and HNF-4alpha genes are unlikely to play a major role in the pathogenesis of late-onset type 2 diabetes in Finnish and Chinese subjects. However, the association of the Ala98Val variant of the HNF-1alpha gene with type 2 diabetes in Finnish subjects may indicate a diabetogenic locus close to the HNF-1alpha gene.

• Authors: J Rissanen, H Wang, R Miettinen, P Kärkkäinen, P Kekäläinen, L Mykkänen, J Kuusisto, P Karhapää, L Niskanen, M Uusitupa, M Laakso
• Journal: Diabetes care (Diabetes Care) Vol. 23 Issue 10 Pg. 1533-8 (Oct 2000) ISSN: 0149-5992 [Print] United States
• PMID: 11023148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• C-Peptide
• DNA-Binding Proteins
• HNF1A protein, human
• HNF1B protein, human
• HNF4A protein, human
• Hepatocyte Nuclear Factor 1-alpha
• Hepatocyte Nuclear Factor 4
• MLX protein, human
• Nuclear Proteins
• Phosphoproteins
• Transcription Factors
• Hepatocyte Nuclear Factor 1
• Hepatocyte Nuclear Factor 1-beta
• Valine
• Alanine

Topics

• Adult
• Age of Onset
• Aged
• Alanine
• Amino Acid Substitution
• Asian People (genetics)
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• C-Peptide (blood)
• China
• DNA-Binding Proteins (genetics)
• Diabetes Mellitus, Type 2 (blood, genetics, physiopathology)
• Exons
• Female
• Finland
• Genetic Variation
• Glucose Tolerance Test
• Hepatocyte Nuclear Factor 1
• Hepatocyte Nuclear Factor 1-alpha
• Hepatocyte Nuclear Factor 1-beta
• Hepatocyte Nuclear Factor 4
• Humans
• Male
• Middle Aged
• Nuclear Proteins
• Phosphoproteins (genetics)
• Polymerase Chain Reaction
• Transcription Factors (genetics)
• Valine
• White People (genetics)