CLINICAL CHARACTERISTICS OF JAPANESE MEN WITH GLUCOKINASE GENE BETA-CELL PROMOTER VARIANT

OBJECTIVE - To study the association between a variant at the position of -30 of beta-cell-specific promoter of the glucokinase gene and glu cose tolerance in the Japanese general population and to assess the cl inical characteristics of subjects with the variant. RESEARCH DESIGN A ND METHODS - The genotype of 657 Japanese men aged 51.0 +/- 8.8 years (mean +/- SD) was analyzed by an allele-specific assay using polymeras e chain reaction-restriction fragment length polymorphism. RESULTS - T he variant allele frequency was 0.188 in subjects with normal glucose tolerance, 0.211 in subjects with impaired glucose tolerance, and 0.17 6 in diabetic subjects. In subjects with fasting plasma glucose levels <140 mg/dl, homozygous subjects for the promoter variant had signific antly higher plasma glucose levels 60 min after oral glucose administr ation when compared with subjects without the variant allele. A cross- sectional analysis showed age-related elevation of basal glucose level s only in subjects without the promoter variant. Individuals heterozyg ous 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 differen ces were not statistically significant. CONCLUSIONS - The beta-cell pr omoter variant in homozygous state was associated with impaired glucos e tolerance, but not with diabetes, and low HDL cholesterol levels in Japanese men. It is unlikely that the glucose intolerance associated w ith the promoter variant is progressive with age.