Variable association between genetic variation in the CYP7 gene promoter and plasma lipoproteins in three Canadian populations.
The promoter sequence variant -278A in the CYP7 gene, which encodes cholesterol 7-alpha hydroxylase, was previously reported to be associated with reduced plasma low density lipoprotein (LDL) cholesterol concentration. We tested for association of CYP7-278A with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 594 Alberta Hutterites, 325 Ontario Oji-Cree and 190 Keewatin Inuit. The CYP7-278A allele frequencies in these three groups were 0.708, 0.466 and 0.490, respectively. The frequencies of CYP7-278A/A homozygotes were 0.481, 0.215 and 0.247, respectively. In the Hutterites, CYP7-278A was associated with reduced plasma HDL-cholesterol and apolipoprotein AI concentration. In the Oji-Cree, CYP7-278A was not significantly associated with any plasma lipoprotein trait. In the Inuit CYP7-278A was associated with elevated plasma total and LDL-cholesterol. There was no consistent relationship between the population mean plasma LDL-cholesterol concentration and the population CYP7-278A frequency. Our findings suggest that the common -278A promoter variant of CYP7 was inconsistently associated with variation in plasma LDL- and HDL-cholesterol in samples from three independent populations. The inconsistencies could be due to differences in genetic background or to unspecified environmental or genetic factors.
Department of Medicine, Blackburn Cardiovascular Genetics Laboratory, John P. Robarts Research Institute, University of Western Ontario, 406-100 Perth Drive, Ont., N6A 5K8, London, Canada. robert.hegele@rri.on.ca
R A
RA
Hegele
J
J
Wang
S B
SB
Harris
J H
JH
Brunt
T K
TK
Young
A J
AJ
Hanley
B
B
Zinman
P W
PW
Connelly
C M
CM
Anderson
D000328:Adult; D000483:Alleles; D002170:Canada / Q000208:ethnology; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D004930:Inuit / Q000235:genetics; D008074:Lipoproteins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics*
D008074:Lipoproteins; D002790:Cholesterol 7-alpha-Hydroxylase