Back to Search Start Over

An ACACB variant implicated in diabetic nephropathy associates with body mass index and gene expression in obese subjects.

Authors :
Lijun Ma
Mariana Murea
James A Snipes
Alejandra Marinelarena
Jacqueline Krüger
Pamela J Hicks
Kurt A Langberg
Meredith A Bostrom
Jessica N Cooke
Daisuke Suzuki
Tetsuya Babazono
Takashi Uzu
Sydney C W Tang
Ashis K Mondal
Neeraj K Sharma
Sayuko Kobes
Peter A Antinozzi
Matthew Davis
Swapan K Das
Neda Rasouli
Philip A Kern
Nathan J Shores
Lawrence L Rudel
Matthias Blüher
Michael Stumvoll
Donald W Bowden
Shiro Maeda
John S Parks
Peter Kovacs
Robert L Hanson
Leslie J Baier
Steven C Elbein
Barry I Freedman
Source :
PLoS ONE, Vol 8, Iss 2, p e56193 (2013)
Publication Year :
2013
Publisher :
Public Library of Science (PLoS), 2013.

Abstract

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n = 858; p-additive = 0.765). Association with BMI was seen in a meta-analysis including all non-T2DM subjects (n = 3568; p-additive = 0.02). Among subjects with T2DM, rs2268388 was not associated with BMI in Japanese (n = 2912) or EAs (n = 1149); however, the T allele associated with higher BMI in the subset with BMI≥30 kg/m(2) (n = 568 EAs; p-additive = 0.049, n = 196 Japanese; p-additive = 0.049). Association with BMI was strengthened in a T2DM meta-analysis that included an additional 756 AAs (p-additive = 0.080) and 48 Hong Kong Chinese (p-additive = 0.81) with BMI≥30 kg/m(2) (n = 1575; p-additive = 0.0033). The effect of rs2268388 on gene expression revealed that the T risk allele associated with higher ACACB messenger levels in adipose tissue (41 EAs and 20 AAs with BMI>30 kg/m(2); p-additive = 0.018) and ACACB protein levels in the liver tissue (mixed model p-additive = 0.03, in 25 EA bariatric surgery patients with BMI>30 kg/m(2) for 75 exams). The T allele also associated with higher hepatic triglyceride levels. These data support a role for ACACB in obesity and potential roles for altered lipid metabolism in susceptibility to DN.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
8
Issue :
2
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.b096f420e3c542b4a42f8262f5ee7a6d
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0056193