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Paul Franks

Paul Franks

Principal investigator

Paul Franks

The Effect of ACACB cis-Variants on Gene Expression and Metabolic Traits

Author

  • Lijun Ma
  • Ashis K. Mondal
  • Mariana Murea
  • Neeraj K. Sharma
  • Anke Toenjes
  • Kurt A. Langberg
  • Swapan K. Das
  • Paul Franks
  • Peter Kovacs
  • Peter A. Antinozzi
  • Michael Stumvoll
  • John S. Parks
  • Steven C. Elbein
  • Barry I. Freedman

Summary, in English

Background: Acetyl Coenzyme A carboxylase beta (ACACB) is the rate-limiting enzyme in fatty acid oxidation, and continuous fatty acid oxidation in Acacb knock-out mice increases insulin sensitivity. Systematic human studies have not been performed to evaluate whether ACACB variants regulate gene expression and insulin sensitivity in skeletal muscle and adipose tissues. We sought to determine whether ACACB transcribed variants were associated with ACACB gene expression and insulin sensitivity in non-diabetic African American (AA) and European American (EA) adults. Methods: ACACB transcribed single nucleotide polymorphisms (SNPs) were genotyped in 105 EAs and 46 AAs whose body mass index (BMI), lipid profiles and ACACB gene expression in subcutaneous adipose and skeletal muscle had been measured. Allelic expression imbalance (AEI) was assessed in lymphoblast cell lines from heterozygous subjects in an additional EA sample (n = 95). Selected SNPs were further examined for association with insulin sensitivity in a cohort of 417 EAs and 153 AAs. Results: ACACB transcribed SNP rs2075260 (A/G) was associated with adipose ACACB messenger RNA expression in EAs and AAs (p = 3.8x10(-5), dominant model in meta-analysis, Stouffer method), with the (A) allele representing lower gene expression in adipose and higher insulin sensitivity in EAs (p = 0.04). In EAs, adipose ACACB expression was negatively associated with age and sex-adjusted BMI (r = -0.35, p = 0.0002). Conclusions: Common variants within the ACACB locus appear to regulate adipose gene expression in humans. Body fat (represented by BMI) may further regulate adipose ACACB gene expression in the EA population.

Department/s

  • Genetic and Molecular Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2011

Language

English

Publication/Series

PLoS ONE

Volume

6

Issue

8

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 1932-6203