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

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.

journal_name

Diabetes

journal_title

Diabetes

authors

Tataranni PA,Baier L,Jenkinson C,Harper I,Del Parigi A,Bogardus C

doi

10.2337/diabetes.50.4.901

subject

Has Abstract

pub_date

2001-04-01 00:00:00

pages

901-4

issue

4

eissn

0012-1797

issn

1939-327X

journal_volume

50

pub_type

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