A common P2 promoter polymorphism of the hepatocyte nuclear factor-4alpha gene is associated with insulin secretion in non-obese Japanese with type 2 diabetes

• Published in: Endocrine journal 2008-01, Vol.55 (6), p.999-1004
• Main Authors: Tokunaga, Ayumi, Horikawa, Yukio, Fukuda-Akita, Etsuko, Okita, Kohei, Iwahashi, Hiromi, Shimomura, Iichiro, Takeda, Jun, Yamagata, Kazuya
• Format: Article
• Language: English
• Subjects: Aged; Case-Control Studies; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Female; Gene Frequency; Genetic Linkage; Genetic Predisposition to Disease; Genotype; Hepatocyte Nuclear Factor 4 - genetics; Humans; Insulin - metabolism; Insulin Secretion; Japan; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.k08e-083

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