Browse

A Single Nucleotide Polymorphism within the Acetyl-Coenzyme A Carboxylase Beta Gene Is Associated with Proteinuria in Patients with Type 2 Diabetes

Cited 69 time in Web of Science Cited 72 time in Scopus
Authors
Maeda, Shiro; Kobayashi, Masa-aki; Araki, Shin-ichi; Babazono, Tetsuya; Bostrom, Meredith A.; Toyoda, Masao; Tarnow, Lise; Gaede, Peter; Ng, Daniel P. K.; Park, Kyong Soo; Shin, Hyoung Doo; Suzuki, Daisuke; Imanishi, Masahito; Kawai, Koichi; Unoki, Hiroyuki; Tsunoda, Tatsuhiko; Yanagimoto, Toru; Ikeda, Minoru; Nakamura, Yusuke; Pedersen, Oluf; Bowden, Donald W.; Parving, Hans-Henrik; Kawamori, Ryuzo; Kaku, Kohei; Iwamoto, Yasuhiko; Kashiwagi, Atsunori; Jorsal, Anders; Hansen, Torben; Umezono, Tomoya; Cooke, Jessica N.; Freedman, Barry I.
Issue Date
2010-02
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS GENETICS; Vol.6 2; e1000842
Abstract
It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 + 4139 C > T, p = 1.4x10(-6), odds ratio = 1.61, 95% confidence interval [CI]: 1.33-1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35x10(-8), odds ratio = 1.61, 95% Cl: 1.35-1.91). Rs2268388 was also associated with type 2 diabetes-associated end-stage renal disease (ESRD) in European Americans (p = 66x10(-4), odds ratio = 1.61, 95% CI: 1.22-2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes.
ISSN
1553-7390
Language
English
URI
https://hdl.handle.net/10371/76576
DOI
https://doi.org/10.1371/journal.pgen.1000842
Files in This Item:
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse