title: TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular disease in statin-treated patients with familial hypercholesterolemia.
abstract: 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.
authors.affiliation: Department of General Internal Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Martina F
authors.initials: MF
authors.lastname: Mohrschladt
authors.forename: Femke
authors.initials: F
authors.lastname: van der Sman-de Beer
authors.forename: Maaike K
authors.initials: MK
authors.lastname: Hofman
authors.forename: Marieke
authors.initials: M
authors.lastname: van der Krabben
authors.forename: Rudi Gj
authors.initials: RG
authors.lastname: Westendorp
authors.forename: August Hm
authors.initials: AH
authors.lastname: Smelt
mesh_terms: 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
chemical_list: 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