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

OBJECTIVE - To determine the role of the hepatocyte nuclear factor (HNF)-1 alpha and HNF-4 alpha genes in the etiology of late-onset type 2 diabetes i n Finnish and Chinese subjects. RESEARCH DESIGN AND METHODS - The whole coding regions of the genes encodin g for HNF-1 alpha and HNF-4 alpha, including similar to 800 bp of the HNF-1 alpha promoter, were investigated in 40 Finnish subjects (fasting C-peptid e 50-570 pmol/l) and 47 Chinese subjects with type 2 diabetes by single-str and conformation polymorphism (SSCP) analysis. Frequencies of the variants of these genes were analyzed by restriction fragment-length polymorphism an alysis in additional samples of 100 Finnish diabetic patients and 82 Finnis h control subjects and in 58 Chinese diabetic patients and 51 Chinese contr ol 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-4 alpha gene in a Chinese diabetic patient. interestingly the A la98Val substitution of the HNF-1 alpha gene occurred at a significantly hi gher frequency in 140 Finnish diabetic patients compared with 82 control su bjects (P = 0.014). The Ala98Val variant was not, however, associated with abnormalities in insulin secretion evaluated by oral and intravenous glucos e tolerance tests in subjects with normal (n = 295) or impaired (n = 38) gl ucose tolerance. CONCLUSIONS - Variants in the HNF-1 alpha and HNF-4 alpha genes are unlikel y 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 var iant of the HNF-1 alpha gene with type 2 diabetes in Finnish subjects may i ndicate a diabetogenic locus close to the HNF-1 alpha gene.