title: Promoter methylation of serotonin transporter gene is associated with obesity measures: a monozygotic twin study.
abstract: OBJECTIVE
  Epigenetic mechanisms are increasingly being recognized as an important factor for obesity. The serotonin transporter gene (SLC6A4) has a critical role in regulating food intake, body weight and energy balance. This study examines the potential association between SLC6A4 promoter methylation and obesity measures in a monozygotic (MZ) twin sample.
  
  
  METHODS
  We studied 84 MZ twin pairs drawn from the Vietnam Era Twin Registry. Obesity measures include body mass index (BMI), body weight, waist circumference (WC) and waist-hip ratio (WHR). The SLC6A4 promoter methylation profile in peripheral blood leukocytes was quantified by bisulfite pyrosequencing. The association between methylation variation and obesity parameters was examined by mixed-model regression and matched pair analysis, adjusting for age, smoking, alcohol consumption, physical activity and total daily energy intake. Multiple testing was controlled using the adjusted false discovery rate (q-value).
  
  
  RESULTS
  Mean methylation level was positively correlated with BMI (r=0.29; P=0.0002), body weight (r=0.31; P<0.0001) and WC (r=0.20; P=0.009), but not WHR. Intra-pair differences in mean methylation were significantly correlated with intra-pair differences in BMI, body weight and WC, but not WHR. On average, a 1% increase in mean methylation was associated with 0.33 kg m(-2) increase in BMI (95% CI: 0.02-0.65; P=0.03), 1.16 kg increase in body weight (95% CI, 0.16-2.16; P=0.02) and 0.78 cm increase in WC (95% CI, 0.05-1.50; P=0.03) after controlling for potential confounders.
  
  
  CONCLUSIONS
  SLC6A4 promoter hypermethylation is significantly associated with an increased prevalence of obesity within a MZ twin study.
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. jinying-zhao@ouhsc.edu
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Goldberg
authors.forename: V
authors.initials: V
authors.lastname: Vaccarino
mesh_terms: D001823:Body Composition / Q000235:genetics; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D019175:DNA Methylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014430:Twins, Monozygotic; D014728:Veterans
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins