The Effect of the Gly16Arg Polymorphism of the ß2-Adrenergic Receptor Gene on Plasma Free Fatty Acid Levels Is Modulated by Physical Activity
Aline Meirhaeghe,
Jian’an Luan,
Paul Selberg-Franks,
Susie Hennings,
Jo Mitchell,
David Halsall,
Stephen O’Rahilly and
Nicholas J. Wareham
Departments of Medicine (A.M., S.O.), Clinical Biochemistry (A.M.,
D.H., S.O.), and Public Health and Primary Care (J.L., P.S.-F., S.H.,
J.M., N.J.W.), University of Cambridge, Cambridge CB2 2SR, United
Kingdom
Address all correspondence and requests for reprints to: Dr. Nicholas J. Wareham, Institute of Public Health, University of Cambridge, Robinson Way, Cambridge CB2 2SR, United Kingdom.
Abstract
The lipolytic effects of catecholamines are mediated through
membersof the ß2-adrenergic receptor (BAR-2) family.
Previousstudies have suggested that genetic variants in the BAR-2 gene
maybe associated with obesity in some populations. To our knowledge,
nostudies have directly examined the effects of this polymorphismon
circulating nonesterified fatty acid (NEFA) levels. To explorethis
issue further, a cohort of 604 Caucasian individuals (aged40–65 yr)
was genotyped for a common polymorphism in theBAR-2 gene (Gly16Arg),
and the relationships between genotype,body mass index (BMI), NEFA,
and lipid levels were examined.Women bearing the Arg16 allele had
higher BMI values (P <0.01) than Gly16Gly women.
Women carriers of the Arg16Arg genotypehad lower fasting plasma NEFAs
(P < 0.01) and greater suppressionof NEFAs
(P < 0.01) after an oral glucose load than women
bearingthe Gly16 allele. In multivariate analysis after adjustmentfor
age, sex, and smoking status, the interaction between theBAR-2
genotype and BMI in determining fasting NEFA concentrationswas
statistically significant (P < 0.05). The
availabilityof objective measures of total energy expenditure in this
populationpermitted the further examination of interactions,
particularlythat between genotype and physical activity. In the
populationas a whole, after adjustment for confounding by age,
smoking,and BMI, the effect of the Arg16Arg genotype on the
suppressionof NEFA levels was modified by physical activity level
(P forinteraction <0.05). These data suggest the
existence in thispopulation of a gene-physical activity interaction on
NEFA levels.
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