The effects of gender and CYP46 and apo E polymorphism on 24S-hydroxycholesterol levels in Alzheimer's patients treated with statins.
To examine the effect of gender and polymorphisms of CYP46 and apo E on plasma levels of 24S-hydroxycholesterol in Alzheimer's disease (AD) patients and to determine whether these factors contribute to the variability in responses to statin treatment. Fifty-three AD patients had measurement of plasma levels of 24S-hydroxycholesterol, plasma and lipoprotein cholesterol and genotyping of CYP46 and apo E. Thirty-nine of the subjects subsequently participated in a statin trial for 6 weeks, and had a repetition of the baseline measurements. Baseline levels of 24S-hydroxycholesterol were higher in women than in men. There was a positive and significant correlation of plasma oxysterol levels with levels of total plasma cholesterol (women: r = .72, P < .0001; men: r = .47, P = .02) and non-HDL cholesterol (women: r = .68, P < .0001; men: r = 0.51, P = .01) (and LDL cholesterol) but not HDL cholesterol levels. There was no association of CYP46 or apo E polymorphisms with plasma levels of 24S-hydroxycholesterol. AD subjects treated with statins had a similar percent reduction in lathosterol, 24S-hydroxycholesterol, total cholesterol and non-HDL (and LDL) cholesterol regardless of gender and polymorphisms of CYP46. Subjects with the 4/4 polymorphism had less reduction in the ratios of 24S-hydroxycholesterol-LDL cholesterol. Women with AD had higher levels of plasma 24S-hydroxycholesterol levels than men. Women also showed a very strong correlation of plasma levels of 24S-hydroxycholesterol-to-total and non-HDL cholesterol. This may suggest that the oxysterol may be an important marker of AD risk instead of total cholesterol, as suggested by others. Polymorphisms of CYP46 or apo E do not explain levels of oxysterol or non-HDL cholesterol or the responsiveness to statin treatment in this study.
Department of Clinical Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9052, USA. Vega@utsouthwestern.edu
Gloria Lena
GL
Vega
Myron
M
Weiner
Heike
H
Kölsch
Klaus
K
von Bergmann
Reinhard
R
Heun
Dieter
D
Lutjohan
Anh
A
Nguyen
Carol
C
Moore
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D000072556:Cholesterol 24-Hydroxylase; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006720:Homozygote; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D011110:Polymorphism, Genetic; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000235:genetics*; D013261:Sterols / Q000097:blood
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013261:Sterols; C044563:24-hydroxycholesterol; D002784:Cholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase