Original Article

International Journal of Obesity (2013) 37, 140–145; doi:10.1038/ijo.2012.8; published online 31 January 2012

Promoter methylation of serotonin transporter gene is associated with obesity measures: a monozygotic twin study

J Zhao1, J Goldberg2,3 and V Vaccarino4

  1. 1Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
  2. 2Seattle Epidemiologic Research & Information Center, Veterans Affairs Office of Research & Development, Seattle, WA, USA
  3. 3Department of Epidemiology, University of Washington, Seattle, WA, USA
  4. 4Department of Epidemiology, Emory University School of Public Health, and Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA

Correspondence: Dr J Zhao, Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. E-mail: jinying-zhao@ouhsc.edu

Received 2 November 2011; Revised 15 December 2011; Accepted 3 January 2012
Advance online publication 31 January 2012





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.



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).



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 0.33kgm−2 increase in BMI (95% CI: 0.02–0.65; P=0.03), 1.16kg increase in body weight (95% CI, 0.16–2.16; P=0.02) and 0.78cm increase in WC (95% CI, 0.05–1.50; P=0.03) after controlling for potential confounders.



SLC6A4 promoter hypermethylation is significantly associated with an increased prevalence of obesity within a MZ twin study.


DNA methylation; serotonin transporter gene; SLC6A4; monozygotic twins

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