REV-ERB ALPHA polymorphism is associated with obesity in the Spanish obese male population

PLoS One. 2014 Aug 4;9(8):e104065. doi: 10.1371/journal.pone.0104065. eCollection 2014.

Abstract

REV-ERB ALPHA has been shown to link metabolism with circadian rhythms. We aimed to identify new polymorphisms in the promoter of REV-ERB ALPHA and tested whether these polymorphisms could be associated with obesity in the Spanish population. Of the 1197 subjects included in our study, 779 were obese (BMI 34.38±3.1 kg/m2) and 418 lean (BMI 23.27±1.5 kg/m2). In the obese group, 469 of the 779 had type 2 diabetes. Genomic DNA from all the subjects was obtained from peripheral blood cells and the genotyping in the REV-ERB ALPHA promoter was analyzed by High Resolution Melting. We found six polymorphisms in the REV-ERB ALPHA promoter and identified rs939347 as a SNP with the highest frequency in the total population. We did not find any association between rs939347 and type 2 diabetes (p = 0.101), but rs939347 was associated with obesity (p = 0.036) with the genotype AA exhibiting higher frequency in the obese (5.2% in total obese vs 2.4% in lean). This association was found only in men (p = 0.031; 6.5% AA-carriers in obese men vs 1.9% AA-carriers in lean men), with no association found in the female population (p = 0.505; 4.4% AA-carriers in obese women vs 2.7% AA-carriers in lean women). Our results suggest that the REV-ERB ALPHA rs939347 polymorphism could modulate body fat mass in men. The present work supports the role of REV-ERB ALPHA in the development of obesity as well as a potential target for the treatment of obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Body Mass Index
  • Circadian Rhythm / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Association Studies*
  • Humans
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / genetics*
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Sex Characteristics
  • Spain

Substances

  • NR1D1 protein, human
  • Nuclear Receptor Subfamily 1, Group D, Member 1

Grants and funding

This work was supported by the EC Seventh Framework Programme theme FP7-HEALTH-2011 (279171), Spanish Ministry of Science and Innovation (SAF 2010-19527), and CIBER de Diabetes y Enfermedades Metabólicas. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.