Linkage of the cholesterol 7alpha-hydroxylase gene and low-density lipoprotein cholesterol conditional on apolipoprotein E association: the National Heart, Lung, and Blood Institute Family Heart Study.
BACKGROUND
Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7alpha-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism.


METHODS
Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used.


RESULTS
The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.


CONCLUSIONS
Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.
Lin
Jing-Ping
JP
Office of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Salt Lake City, UT 84108-3528, USA. linj@nhlbi.nih.gov
Myers
Richard H
RH
Almasy
Laura
L
Coon
Hilary H
HH
Arnett
Donna K
DK
Hong
Yuling
Y
Hunt
Steven C
SC
D000328:Adult; D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000235:genetics; D012307:Risk Factors
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D011973:Receptors, LDL; D002790:Cholesterol 7-alpha-Hydroxylase