Absence of association between genetic variation of the beta 3-adrenergic receptor and metabolic phenotypes in Oji-Cree.
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.


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.
Hegele
R A
RA
Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, Ontario, Canada. robert.hegele@rri.on.ca
Harris
S B
SB
Hanley
A J
AJ
Azouz
H
H
Connelly
P W
PW
Zinman
B
B
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000483:Alleles; D044467:American Indian or Alaska Native / Q000235:genetics*; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D001824:Body Constitution; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D010641:Phenotype; D011943:Receptors, Adrenergic, beta / Q000235:genetics*
D001786:Blood Glucose; D007328:Insulin; D011943:Receptors, Adrenergic, beta