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

Ma, Lijun; Mondal, Ashis K.; Murea, Mariana; Sharma, Neeraj K.; Toenjes, Anke; Langberg, Kurt A.; Das, Swapan K.; Franks, Paul LU ; Kovacs, Peter and Antinozzi, Peter A., et al. (2011) In PLoS ONE 6(8).
Abstract
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... (More)
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. (Less)
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PLoS ONE
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6
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8
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Public Library of Science
external identifiers
  • wos:000294298800020
  • scopus:80052041654
ISSN
1932-6203
DOI
10.1371/journal.pone.0023860
language
English
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yes
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48dcb9d0-3690-4be7-abbf-6efc3e44b040 (old id 2159115)
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2011-10-03 08:29:29
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2017-11-19 03:44:45
@article{48dcb9d0-3690-4be7-abbf-6efc3e44b040,
  abstract     = {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.},
  articleno    = {e23860},
  author       = {Ma, Lijun and Mondal, Ashis K. and Murea, Mariana and Sharma, Neeraj K. and Toenjes, Anke and Langberg, Kurt A. and Das, Swapan K. and Franks, Paul and Kovacs, Peter and Antinozzi, Peter A. and Stumvoll, Michael and Parks, John S. and Elbein, Steven C. and Freedman, Barry I.},
  issn         = {1932-6203},
  language     = {eng},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {The Effect of ACACB cis-Variants on Gene Expression and Metabolic Traits},
  url          = {http://dx.doi.org/10.1371/journal.pone.0023860},
  volume       = {6},
  year         = {2011},
}