著作: Kunika Kiyoshi/[棚橋 俊仁]/[工藤 英治]/[水澤 典子]/Ichiishi Eiichiro/Nakamura Naoto/[吉川 敏一]/[山岡 孝]/Yasumo Hiroaki/Tsugaw Kazue/[森谷 眞紀]/[井上 寛]/[板倉 光夫]/Effect of +36T > C in intron 1 on the glutamine: fructose-6-phosphate amidotransferase 1 gene and its contribution to type 2 diabetes in different populations./[Journal of Human Genetics]
(英) Effect of +36T > C in intron 1 on the glutamine: fructose-6-phosphate amidotransferase 1 gene and its contribution to type 2 diabetes in different populations.
(英) Glutamine: fructose-6-phosphate amidotransferase 1 (GFPT1) acts as a rate-limiting enzyme in the hexosamine biosynthetic pathway, which is an alternative branch of glucose metabolism. To evaluate GFPT1 as a susceptibility gene to type 2 diabetes, we surveyed the polymorphisms related with the gene function of GFPT1 and assessed its contribution to type 2 diabetes with a case-control association study. Screening of the 5'-flanking and all coding regions of GFPT1 revealed eight polymorphisms, one in the 5'-flanking region, one synonymous polymorphism in exon 8, five in introns and one in 3'-UTR, but no mis-sense or non-sense polymorphism. With in silico simulation, a putative promoter region was apparently predicted between 1 kb upstream and 1 kb downstream of the start codon. In this region, +36T>C polymorphism was located on the GC box sequence in intron 1, and its functional effect on promoter activity was confirmed by luciferase reporter assay, introducing a new functional polymorphism of the GFPT1 gene. To examine its association with type 2 diabetes, we analyzed 2,763 Japanese (1,461 controls and 1,302 cases) and 330 Caucasians (190 controls and 140 cases). One possible association of +36T>C was observed in Caucasians, but no association of polymorphisms including +36T>C in intron 1 or haplotypes was observed in Japanese. Although we could not completely rule out a contribution to specific sub-groups or other populations, genetic variation of GFPT1 is unlikely to have a major role in the susceptibility to type 2 diabetes in Japanese.
Journal of Human Genetics(日本人類遺伝学会)
|年月日||必須||2006年 9月 26日|