title: Clinical characteristics of double heterozygotes with familial hypercholesterolemia and cholesteryl ester transfer protein deficiency.
abstract: Coronary heart disease (CHD) in familial hypercholesterolemia (FH) may be modified by genetic and/or environmental factors. We described the effect of the cholesteryl ester transfer protein (CETP) gene on CHD in heterozygous FH caused by low density lipoprotein receptor (LDL-R) gene mutation. In 288 unrelated Japanese subjects with heterozygous FH, the allele frequency of an intron 14 G(+1)-to-A mutation (Int14 A) and a missense mutation in exon 15 (Asp442 to Gly, D442G) was 0.3 and 3.0%, respectively. HDL-C levels (1.55 +/- 0.08 mmol/l) in FH patients with heterozygous CETP deficiency were higher than those (1.19 +/- 0.08 mmol/l) in FH without CETP deficiency (P < 0.03), while LDL-C levels in FH with CETP deficiency were moderately reduced. However, two FH patients with CETP deficiency suffered myocardial infarction, and six patients had effort angina pectoris and/or coronary atherosclerosis. No difference in the score of coronary stenosis index (CSI) was found in FH with/without CETP deficiency, although CSI was inversely correlated with HDL-C levels (P < 0.05). Thus, the effect of increased HDL-C levels caused by partial deficiency of CETP is insufficient to prevent CHD in FH.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Haraki
authors.forename: A
authors.initials: A
authors.lastname: Inazu
authors.forename: K
authors.initials: K
authors.lastname: Yagi
authors.forename: K
authors.initials: K
authors.lastname: Kajinami
authors.forename: J
authors.initials: J
authors.lastname: Koizumi
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D003327:Coronary Disease / Q000235:genetics; D005260:Female; D006023:Glycoproteins; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins