Lund University is celebrating 350 years. Read more on lunduniversity.lu.se

Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

Evaluation of A2BP1 as an Obesity Gene

Author:
  • Lijun Ma
  • Robert L. Hanson
  • Michael T. Traurig
  • Yunhua L. Muller
  • Bakhshish P. Kaur
  • Jessica M. Perez
  • David Meyre
  • Mao Fu
  • Antje Koerner
  • Paul Franks
  • Wieland Kiess
  • Sayuko Kobes
  • William C. Knowler
  • Peter Kovacs
  • Philippe Froguel
  • Alan R. Shuldiner
  • Clifton Bogardus
  • Leslie J. Baler
Publishing year: 2010
Language: English
Pages: 2837-2845
Publication/Series: Diabetes
Volume: 59
Issue: 11
Document type: Journal article
Publisher: American Diabetes Association

Abstract english

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

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Endocrinology
  • ISSN: 1939-327X
Paul Franks
E-mail: paul.franks [at] med.lu.se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49

60-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00