Tokunaga Ayumi, Horikawa Yukio, Fukuda-Akita Etsuko, Okita Kohei, Iwahashi Hiromi, Shimomura Iichiro, Takeda Jun, Yamagata Kazuya
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Endocr J. 2008 Dec;55(6):999-1004. doi: 10.1507/endocrj.k08e-083. Epub 2008 Jul 24.
Heterozygous mutations of the hepatocyte nuclear factor (HNF)-4alpha gene cause a particular form of maturity-onset diabetes of the young (MODY1). Recent genetic studies have shown that single nucleotide polymorphisms (SNPs) of the beta-cell type P2 promoter of the HNF-4alpha gene are associated with type 2 diabetes in some populations. In the Japanese population, a haplotype consisting of two SNPs (rs1884614 and rs2144908) in the P2 promoter region is reported to show a significant association with type 2 diabetes.
Both rs1884614 and rs2144908 were genotyped in 349 type 2 diabetic patients and 203 non-diabetic controls. The relation of these SNPs to clinical characteristics was also examined in the diabetic subjects.
There were no differences in the genotype distribution of the two SNPs between the control and diabetic subjects, and the haplotype distribution was also similar in the two groups. However, the rs1884614 T/T genotype was significantly associated with a smaller area under the plasma insulin curve (AUC) during the OGTT in non-obese (BMI <25 kg/m(2)) patients (p=0.0272; adjusted for age and sex).
SNP rs1884614 in the P2 promoter region of the HNF-4alpha gene may influence insulin secretion in non-obese Japanese subjects with type 2 diabetes.
肝细胞核因子（HNF）-4α基因的杂合突变会导致一种特殊形式的青年发病型糖尿病（MODY1）。近期的遗传学研究表明，HNF-4α基因β细胞型P2启动子的单核苷酸多态性（SNP）在某些人群中与2型糖尿病相关。在日本人群中，据报道P2启动子区域由两个SNP（rs1884614和rs2144908）组成的单倍型与2型糖尿病存在显著关联。
对349例2型糖尿病患者和203例非糖尿病对照者进行rs1884614和rs2144908基因分型。还在糖尿病受试者中研究了这些SNP与临床特征之间的关系。
对照者和糖尿病患者之间这两个SNP的基因型分布没有差异，两组的单倍型分布也相似。然而，rs1884614 T/T基因型与非肥胖（BMI<25 kg/m²）患者口服葡萄糖耐量试验（OGTT）期间血浆胰岛素曲线下面积（AUC）较小显著相关（p = 0.0272；经年龄和性别校正）。
HNF-4α基因P2启动子区域的SNP rs1884614可能会影响非肥胖的日本2型糖尿病患者的胰岛素分泌。
