title: The effect of ACACB cis-variants on gene expression and metabolic traits.
abstract: BACKGROUND
  Acetyl Coenzyme A carboxylase β (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 = 3.8×10(-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.
authors: Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America. lima@wfubmc.edu
authors: Lijun
authors: L
authors: Ma
authors: Ashis K
authors: AK
authors: Mondal
authors: Mariana
authors: M
authors: Murea
authors: Neeraj K
authors: NK
authors: Sharma
authors: Anke
authors: A
authors: Tönjes
authors: Kurt A
authors: KA
authors: Langberg
authors: Swapan K
authors: SK
authors: Das
authors: Paul W
authors: PW
authors: Franks
authors: Peter
authors: P
authors: Kovacs
authors: Peter A
authors: PA
authors: Antinozzi
authors: Michael
authors: M
authors: Stumvoll
authors: John S
authors: JS
authors: Parks
authors: Steven C
authors: SC
authors: Elbein
authors: Barry I
authors: BI
authors: Freedman
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D044383:Black People / Q000235:genetics; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D008660:Metabolism / Q000235:genetics*; D008875:Middle Aged; D018482:Muscle, Skeletal; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D000103:Acetyl-CoA Carboxylase