Elevated HDL cholesterol is a risk factor for ischemic heart disease in white women when caused by a common mutation in the cholesteryl ester transfer protein gene.
BACKGROUND
The level of HDL cholesterol is inversely related to the risk of ischemic heart disease.


RESULTS
In 9168 women and men from a general population and 946 women and men with ischemic heart disease (all white), we tested the hypothesis that the Ile405Val mutation in the cholesteryl ester transfer protein gene (CETP) affects HDL cholesterol levels and the risk of ischemic heart disease. The relative frequencies of Ile/Ile, Ile/Val, and Val/Val carriers were 0.46, 0.43, and 0.11 for both women and men. Women with these 3 genotypes had mean HDL cholesterol levels of 1.68, 1.75, and 1.82 mmol/L, respectively (P<0.001, ANOVA), as well as a significant decrease in the ratio of total to HDL cholesterol (P=0. 002, ANOVA). On multiple logistic regression analysis, women not treated with hormone replacement therapy who were heterozygous or homozygous for Val405 had a 1.4-fold (95% CI 1.0 to 1.9) to 2.1-fold (95% CI 1.3 to 3.4) increase in the risk of ischemic heart disease. No significant associations were found in men.


CONCLUSIONS
Increased HDL cholesterol levels caused by mutations in CETP are associated with an increased risk of ischemic heart disease in white women.
Agerholm-Larsen
B
B
Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
Nordestgaard
B G
BG
Steffensen
R
R
Jensen
G
G
Tybjaerg-Hansen
A
A
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006023:Glycoproteins; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D017354:Point Mutation; D017698:Postmenopause; D017697:Premenopause; D012307:Risk Factors; D017678:Sex Distribution; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D014280:Triglycerides