Clinical Characteristics of Japanese Men With Glucokinase Gene β-cell Promoter Variant
Clinical Characteristics of Japanese Men With Glucokinase Gene β-cell Promoter Variant
复制标题
具有葡萄糖激酶基因β细胞启动子变异的日本男性的临床特征
作者：
Kentaro Yamada;Xiaohong Yuan;Satomi Ishiyama;F. Ichikawa;Ken;Atsuko Koyanagi;W. Koyama;K. Nonaka
目的研究葡萄糖激酶基因β细胞特异性启动子-30位点变异与日本普通人群葡萄糖耐量的关系，并评估该变异受试者的临床特征。研究设计和方法：采用聚合酶链反应-限制性片段长度多态性等位基因特异性分析方法，分析657名年龄为51.0 ± 8.8岁（平均值±标准差）的日本男性的基因型。结果糖耐量正常组、糖耐量减低组和糖尿病组的变异等位基因频率分别为0.188、0.211和0.176。在空腹血糖水平<140 mg/dl的受试者中，启动子变体的纯合子受试者在口服葡萄糖后60 min的血糖水平显著高于无变体等位基因的受试者。一项横断面分析显示，与年龄相关的基础葡萄糖水平升高仅发生在没有启动子变异的受试者中。该变异体杂合子个体的HDL胆固醇水平显著低于正常受试者。高密度脂蛋白胆固醇值在纯合子的人低于正常和杂合子的受试者，虽然差异没有统计学意义。结论：在日本男性中，纯合状态的β细胞启动子变异与糖耐量受损相关，但与糖尿病和低HDL胆固醇水平无关。与启动子变异相关的葡萄糖耐受不良不太可能随着年龄的增长而进展。
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.
DOI：
10.1073/pnas.89.16.7698
发表时间：
1992-08-15
影响因子：
11.1
作者：
STOFFEL, M;FROGUEL, P;BELL, GI
通讯作者：
BELL, GI
影响因子：
158.5
作者：
FROGUEL, P;ZOUALI, H;COHEN, D
通讯作者：
COHEN, D
影响因子：
7.1
作者：
TSUNEHARA, CH;LEONETTI, DL;FUJIMOTO, WY
通讯作者：
FUJIMOTO, WY