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Evaluation of A2BP1 as an Obesity Gene

Ma, Lijun; Hanson, Robert L.; Traurig, Michael T.; Muller, Yunhua L.; Kaur, Bakhshish P.; Perez, Jessica M.; Meyre, David; Fu, Mao; Koerner, Antje and Franks, Paul LU , et al. (2010) In Diabetes 59(11). p.2837-2845
Abstract
OBJECTIVE-A genome-wide association study (GWAS) in Pima Indians (n = 413) identified variation in the ataxin-2 binding protein 1 gene (A2BP1) that was associated with percent body fat. On the basis of this association and the obese phenotype of ataxin-2 knockout mice, A2BP1 was genetically and functionally analyzed to assess its potential role in human obesity. RESEARCH DESIGN AND METHODS-Variants spanning A2BP1 were genotyped in a population-based sample of 3,234 full-heritage Pima Indians, 2,843 of whom were not part of the initial GWAS study and therefore could serve as a sample to assess replication. Published GWAS data across A2BP1 were additionally analyzed in French adult (n = 1,426) and children case/control subjects (n = 1,392)... (More)
OBJECTIVE-A genome-wide association study (GWAS) in Pima Indians (n = 413) identified variation in the ataxin-2 binding protein 1 gene (A2BP1) that was associated with percent body fat. On the basis of this association and the obese phenotype of ataxin-2 knockout mice, A2BP1 was genetically and functionally analyzed to assess its potential role in human obesity. RESEARCH DESIGN AND METHODS-Variants spanning A2BP1 were genotyped in a population-based sample of 3,234 full-heritage Pima Indians, 2,843 of whom were not part of the initial GWAS study and therefore could serve as a sample to assess replication. Published GWAS data across A2BP1 were additionally analyzed in French adult (n = 1,426) and children case/control subjects (n = 1,392) (Meyre et al. Nat Genet 2009;41:157-159). Selected variants were genotyped in two additional samples of Caucasians (Amish, n = 1,149, and German children case/control subjects, n = 998) and one additional Native American (n = 2,531) sample. Small interfering RNA was used to knockdown A2bp1 message levels in mouse embryonic hypothalamus cells. RESULTS-No single variant in A2BP1 was reproducibly associated with obesity across the different populations. However, different variants within intron 1 of A2BP1 were associated with BMI in full-heritage Pima Indians (rs10500331, P = 1.9 x 10(-7)) and obesity in French Caucasian adult (rs4786847, P = 1.9 x 10(-10)) and children (rs8054147, P = 9.2 x 10(-6)) case/control subjects. Reduction of A2bp1 in mouse embryonic hypothalamus cells decreased expression of Atxn2, Insr, and Mc4r. CONCLUSIONS-Association analysis suggests that variation in A2BP1 influences obesity, and functional studies suggest that A2BP1 could potentially affect adiposity via the hypothalamic MC4R pathway. Diabetes 59:2837-2845, 2010 (Less)
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published
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Diabetes
volume
59
issue
11
pages
2837 - 2845
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000284133400020
  • scopus:78049245904
ISSN
1939-327X
DOI
10.2337/db09-1604
language
English
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yes
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7f976ac1-a0da-44e2-b7fa-61d4383d3c02 (old id 1752218)
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2011-01-04 07:43:16
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2018-05-29 11:29:14
@article{7f976ac1-a0da-44e2-b7fa-61d4383d3c02,
  abstract     = {OBJECTIVE-A genome-wide association study (GWAS) in Pima Indians (n = 413) identified variation in the ataxin-2 binding protein 1 gene (A2BP1) that was associated with percent body fat. On the basis of this association and the obese phenotype of ataxin-2 knockout mice, A2BP1 was genetically and functionally analyzed to assess its potential role in human obesity. RESEARCH DESIGN AND METHODS-Variants spanning A2BP1 were genotyped in a population-based sample of 3,234 full-heritage Pima Indians, 2,843 of whom were not part of the initial GWAS study and therefore could serve as a sample to assess replication. Published GWAS data across A2BP1 were additionally analyzed in French adult (n = 1,426) and children case/control subjects (n = 1,392) (Meyre et al. Nat Genet 2009;41:157-159). Selected variants were genotyped in two additional samples of Caucasians (Amish, n = 1,149, and German children case/control subjects, n = 998) and one additional Native American (n = 2,531) sample. Small interfering RNA was used to knockdown A2bp1 message levels in mouse embryonic hypothalamus cells. RESULTS-No single variant in A2BP1 was reproducibly associated with obesity across the different populations. However, different variants within intron 1 of A2BP1 were associated with BMI in full-heritage Pima Indians (rs10500331, P = 1.9 x 10(-7)) and obesity in French Caucasian adult (rs4786847, P = 1.9 x 10(-10)) and children (rs8054147, P = 9.2 x 10(-6)) case/control subjects. Reduction of A2bp1 in mouse embryonic hypothalamus cells decreased expression of Atxn2, Insr, and Mc4r. CONCLUSIONS-Association analysis suggests that variation in A2BP1 influences obesity, and functional studies suggest that A2BP1 could potentially affect adiposity via the hypothalamic MC4R pathway. Diabetes 59:2837-2845, 2010},
  author       = {Ma, Lijun and Hanson, Robert L. and Traurig, Michael T. and Muller, Yunhua L. and Kaur, Bakhshish P. and Perez, Jessica M. and Meyre, David and Fu, Mao and Koerner, Antje and Franks, Paul and Kiess, Wieland and Kobes, Sayuko and Knowler, William C. and Kovacs, Peter and Froguel, Philippe and Shuldiner, Alan R. and Bogardus, Clifton and Baler, Leslie J.},
  issn         = {1939-327X},
  language     = {eng},
  number       = {11},
  pages        = {2837--2845},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Evaluation of A2BP1 as an Obesity Gene},
  url          = {http://dx.doi.org/10.2337/db09-1604},
  volume       = {59},
  year         = {2010},
}