A common mutation of cholesteryl ester transfer protein gene in dialysis patients.
BACKGROUND
In patients on maintenance hemodialysis, a decreased concentration of high-density lipoprotein cholesterol (HDL-C) is an apparent independent risk factor for vascular disease (VD). A common missense mutation of cholesteryl ester transfer protein (CETP) gene, D442G (Asp442 to Gly), increases HDL-C levels, but the mutation may also diminish the activity of reverse cholesterol transport.


METHODS
We compared the genotype distribution of the D442G polymorphism and postprandial serum lipid levels between patients with and without VD in 414 hemodialysis patients.


RESULTS
Serum levels of total cholesterol and HDL-C did not differ in patients with the mutation [group M (+)] and without the mutation [group M (-)] and in patients with and without VD. However, patients with below median HDL-C levels (< 45 mg/dl) had a significantly higher prevalence of VD than those with above median HDL levels (26.0 vs. 15.2%, P < 0.01). Moreover, in this low-HDL-C subgroup, group M (+) patients had a significantly higher prevalence of VD than group M (-) patients (54.5 vs. 24.4%, P < 0.05). In the subgroup, group M (+) patients with VD had higher levels of total cholesterol and a higher atherogenic index than those without VD, whereas group M (-) patients with VD had lower levels of total cholesterol and a lower atherogenic index than those without VD.


CONCLUSIONS
The D442G mutation may be a risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl. Atherogenic lipid profiles may promote atherosclerosis in the patients with the mutation, but not in those with no mutation.
Department of Clinical and Laboratory Medicine, Faculty of Medicine, Fukui Medical University, Japan. hkimura@fmsrsa.fukui-med.ac.jp
H
H
Kimura
F
F
Gejyo
S
S
Suzuki
T
T
Yamaguchi
T
T
Imura
R
R
Miyazaki
K
K
Ei
I
I
Ei
M
M
Oda
Y
Y
Miyakawa
M
M
Arakawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D006435:Renal Dialysis; D012307:Risk Factors; D014652:Vascular Diseases / Q000097:blood / Q000235:genetics
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins