Diabetes Care, Vol 21, Issue 5 851-854, Copyright © 1998 by American Diabetes Association
Absence of association between genetic variation of the beta 3-adrenergic receptor and metabolic phenotypes in Oji-Cree
RA Hegele, SB Harris, AJ Hanley, H Azouz, PW Connelly and B Zinman
Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, Ontario, Canada. robert.hegele@rri.on.ca
OBJECTIVE: To assess the association between the common missense variant,
Y64R, in the gene encoding the beta 3-adrenergic receptor, ADRB3, and
intermediate phenotypes related to obesity and NIDDM in Canadian Oji-Cree.
RESEARCH DESIGN AND METHODS: We determined genotypes of the ADRB3 Y64R
polymorphism in 508 clinically and biochemically well-characterized adult
Oji-Cree, of whom 115 had NIDDM. We tested for associations with
multivariate analysis of variance. RESULTS: We found the ADRB3 R64 allele
frequency to be 0.40 in this population, which is the highest yet observed
in a human population. Furthermore, 15% of subjects were R64/R64
homozygotes, compared with a virtual absence of homozygotes in European
study samples. However, we found no statistically significant associations
of the ADRB3 Y64R genotype either with the presence of NIDDM, with indexes
of obesity, or with intermediate quantitative biochemical traits related to
NIDDM. CONCLUSIONS: Despite the very high frequency of the ADRB3 R64 allele
in this sample of aboriginal people, it was not associated with any
metabolic phenotype. This suggests that the ADRB3 R64 allele is probably
not a major determinant of obesity or NIDDM in these aboriginal Canadians.