The Ala/Va198 polymorphism of the hepatocyte nuclear factor-1α gene contributes to the interindividual variation in serum C-peptide response during an oral glucose tolerance test: Evidence from studies of 231 glucose- tolerant first degree relatives of type 2 diabetic probands
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The third form of maturity-onset diabetes of the young is caused by mutations in the hepatocyte nuclear factor-1α gene. Recently, we demonstrated an association between a prevalent polymorphism at codon 98, Ala/Val98, of this gene and a 20% decreased insulin release during an oral glucose tolerance test (OGTT) in middle-aged glucose-tolerant Danish Caucasian subjects. The major objective of the present study was to replicate this finding among glucose-tolerant first degree relatives of type 2 diabetic patients of the same ethnic origin. All participants, 231 glucose-tolerant offspring of 62 type 2 diabetic probands, underwent an OGTT with measurements of plasma glucose, serum insulin, and serum C peptide during the test. Thirty-three heterozygous carriers of the Ala/Val variant were identified, whereas no subjects had the variant in its homozygous form. Ala/Val carriers had a 20% reduction in serum C peptide at 30 min during the OGTT (1225 ± 636 vs. 1507 ± 624 pmol/L; P = 0.02) compared to wild-type carriers. No significant differences in serum insulin levels during the OGTT were observed between carriers of the variant and Ala/Ala homozygotes. In conclusion, among Danish glucose-tolerant first degree relatives of type 2 diabetic patents the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1α gene is associated with a decreased serum C-peptide secretion during an OGTT. This finding confirms our previously reported observation of the functional importance of the variant to insulin secretion during an OGTT among middle- aged healthy subjects.
|Journal||Journal of Clinical Endocrinology and Metabolism|
|Number of pages||4|
|Publication status||Published - 1 Dec 1998|