A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure

P. Antonio Tataranni, Leslie Baier, Chris Jenkinson, Inge Harper, Angelo Del Parigi, Clifton Bogardus

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Abstract

Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. We hypothesized that the Ser311Cys mutation of DRD2 may inhibit energy expenditure. Here we report that total energy expenditure (doubly labeled water) measured in 89 nondiabetic Pima Indians was 244 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.056). The 24-h resting energy expenditure (respiratory chamber) measured in 320 nondiabetic Pimas was also 87 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.026). These findings are the first evidence that a genetic mutation is associated with reduced energy expenditure in humans. Because the impact of this mutation on human obesity is small, we suggest that either the energy deficit induced is not large enough to significantly influence body weight in this population and/or that the Cys311-encoding allele is also associated with reduced energy intake.

Original languageEnglish (US)
Pages (from-to)901-904
Number of pages4
JournalDiabetes
Volume50
Issue number4
DOIs
StatePublished - Jan 1 2001

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Tataranni, P. A., Baier, L., Jenkinson, C., Harper, I., Del Parigi, A., & Bogardus, C. (2001). A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure. Diabetes, 50(4), 901-904. https://doi.org/10.2337/diabetes.50.4.901