title: SH2B1 CpG-SNP is associated with body weight reduction in obese subjects following a dietary restriction program.
abstract: The objective of this study was to examine whether 7 SNPs previously associated with obesity-related traits that add or remove potential sites of DNA methylation are accompanied by differential DNA methylation and subsequently affect adiposity variables or body weight reduction in WBC from obese subjects under an energy-restricted program.
  
  
  METHODS
  Anthropometric measurements were assessed in 47 volunteers recruited within the RESMENA study (Spain). At baseline, DNA from white blood cells was isolated and 7 obesity-related trait CpG-SNPs were genotyped by TaqMan-PCR. Then, methylation levels of CpG-SNP sites were quantified by MassArray® EpiTyper™ or MS-HRM approaches.
  
  
  RESULTS
  Differential DNA methylation levels were observed by genotypes in all of the CpG-SNPs analyzed. The FTO and BDNF methylation levels were further correlated with baseline body weight and, BDNF mRNA levels and body weight change, respectively. Moreover, the rs7359397 (SH2B1) was associated with the body weight, body mass index, and truncal fat mass reduction.
  
  
  CONCLUSIONS
  Our results reveal the interaction of epigenetic and genetic variations in CpG-SNPs, especially in BDNF and SH2B1 genes, and how allele-specific methylation may contribute to elucidate the possible molecular mechanisms as these SNPs are affecting the decrease of mRNA levels and contributing to a lower body weight reduction.
authors.affiliation: CIBERobn, Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mansego
authors.forename: Fermin Ignacio
authors.initials: FI
authors.lastname: Milagro
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Zulet
authors.forename: José Alfredo
authors.initials: JA
authors.lastname: Martinez
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D050154:Adiposity / Q000235:genetics; D000328:Adult; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger; D015431:Weight Loss / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; C518910:SH2B1 protein, human