OBJECTIVE

To study the association between a variant at the position of −30 of β-cell-specific promoter of the glucokinase gene and glucose tolerance in the Japanese general population and to assess the clinical characteristics of subjects with the variant.

RESEARCH DESIGN AND METHODS

The genotype of 657 Japanese men aged 51.0 ± 8.8 years (mean ± SD) was analyzed by an allele-specific assay using polymerase chain reaction-restriction fragment length polymorphism.

RESULTS

The variant allele frequency was 0.188 in subjects with normal glucose tolerance, 0.211 in subjects with impaired glucose tolerance, and 0.176 in diabetic subjects. In subjects with fasting plasma glucose levels <140 mg/dl, homozygous subjects for the promoter variant had significantly higher plasma glucose levels 60 min after oral glucose administration when compared with subjects without the variant allele. A cross-sectional analysis showed age-related elevation of basal glucose levels only in subjects without the promoter variant. Individuals heterozygous for the variant had significantly lower levels of HDL cholesterol than normal subjects. HDL cholesterol values were lower in homozygous people than in normal and heterozygous subjects, although the differences were not statistically significant.

CONCLUSIONS

The β-cell promoter variant in homozygous state was associated with impaired glucose tolerance, but not with diabetes, and low HDL cholesterol levels in Japanese men. It is unlikely that the glucose intolerance associated with the promoter variant is progressive with age.

This content is only available via PDF.