TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular disease in statin-treated patients with familial hypercholesterolemia.
The effects of TaqI restriction fragment length polymorphism of the CETP gene on the occurrence of cardiovascular disease (CVD) events were investigated in patients with familial hypercholesterolemia (FH). A total of 300 FH patients, of which 116 (39%) had CVD at the start of the study, were treated with statins during a mean period of 8.5 years. The distribution of Taq1B genotypes was 31% B1B1, 49% B1B2, and 20% B2B2. No differences were found at baseline between the three genotypes, except for an association of the B1 allele with lower high-density lipoprotein (HDL)-cholesterol levels (P=0.003). All patients were put on statins within 6-8 weeks after the first visit; about 60% received simvastatin (20-40 mg daily) and 40% either pravastatin (40 mg daily) or atorvastatin (20-40 mg daily). The different statin treatments were similar for all groups. The mean change of plasma HDL-cholesterol, low-density lipoprotein-cholesterol, and triglyceride concentration during statin therapy was similar for the three genotypes. During follow-up, new CVD events were recorded in 22 (37%) of the B2B2 patients (n=59) and in 67 (28%) of B1 allele carriers (n=241) (P=0.36). The relative risk for CVD events, after adjustment for age, gender, and CVD at intake, was 1.8 (CI: 1.1-3.0) for B2B2 carriers compared to B1 allele carriers. The Taq1B polymorphism is a significant predictor of future CVD events in statin-treated patients with FH. In spite of similar improvement of the lipoprotein profile during statin therapy, our FH patients with the B2B2 genotype may have a higher CVD risk in comparison with the B1 allele carriers.
Mohrschladt
Martina F
MF
Department of General Internal Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
van der Sman-de Beer
Femke
F
Hofman
Maaike K
MK
van der Krabben
Marieke
M
Westendorp
Rudi Gj
RG
Smelt
August Hm
AH
D000293:Adolescent; D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases