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.
Hegele
R A
RA
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
Wang
J
J
Harris
S B
SB
Brunt
J H
JH
Young
T K
TK
Hanley
A J
AJ
Zinman
B
B
Connelly
P W
PW
Anderson
C M
CM
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