Genes implicated in serotonergic and dopaminergic functioning predict BMI categories

Obesity (Silver Spring). 2008 Feb;16(2):348-55. doi: 10.1038/oby.2007.65.

Abstract

Objective: This study addressed the hypothesis that variation in genes associated with dopamine function (SLC6A3, DRD2, DRD4), serotonin function (SLC6A4, and regulation of monoamine levels (MAOA) may be predictive of BMI categories (obese and overweight + obese) in young adulthood and of changes in BMI as adolescents transition into young adulthood. Interactions with gender and race/ethnicity were also examined.

Methods and procedures: Participants were a subsample of individuals from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset of 1,584 unrelated individuals with genotype data. Multiple logistic regressions were conducted to evaluate the associations between genotypes and obesity (BMI > 29.9) or overweight + obese combined (BMI > or = 25) with normal weight (BMI = 18.5-24.9) as a referent. Linear regression models were used to examine change in BMI from adolescence to young adulthood.

Results: Significant associations were found between SLC6A4 5HTTLPR and categories of BMI, and between MAOA promoter variable number tandem repeat (VNTR) among men and categories of BMI. Stratified analyses revealed that the association between these two genes and excess BMI was significant for men overall and for white and Hispanic men specifically. Linear regression models indicated a significant effect of SLC6A4 5HTTLPR on change in BMI from adolescence to young adulthood.

Discussion: Our findings lend further support to the involvement of genes implicated in dopamine and serotonin regulation on energy balance.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aging / ethnology
  • Aging / genetics
  • Aging / metabolism
  • Body Mass Index*
  • Cohort Studies
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • European Continental Ancestry Group
  • Female
  • Hispanic Americans
  • Humans
  • Logistic Models
  • Longitudinal Studies
  • Male
  • Monoamine Oxidase / genetics*
  • Monoamine Oxidase / metabolism
  • Obesity / ethnology
  • Obesity / genetics*
  • Obesity / physiopathology
  • Predictive Value of Tests
  • Receptors, Dopamine D4 / genetics
  • Receptors, Dopamine D4 / metabolism
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Sex Characteristics

Substances

  • DRD4 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A3 protein, human
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Receptors, Dopamine D4
  • Serotonin
  • Monoamine Oxidase
  • Dopamine