title: [Molecular genetics of cholesterol transport and cholesterol reverse transport disorders (familial hypercholesterolemia and CETP deficiency), and coronary heart disease].
abstract: Familial hypercholesterolemia (FH) is a disorder of LDL receptor abnormalities, and the resultant high-LDL-cholesterolemia produces atherosclerosis. More than 150 different mutations in the LDL receptor gene have been reported in the world. Seven variants of the LDL receptor gene have been identified in our laboratory. These seven mutants in 85 patients from 31 families accounted for only 15.5% of the FH cases. LDL receptor gene abnormalities are highly heterogenous in Japan, and the variation of the LDL receptor mutant may determine the severity of hypercholesterolemia and coronary heart disease in FH. A serum HDL above 60 mg/dl is a negative risk factor for coronary atherosclerosis. We found that familial hyperalphalipoproteinemia can be produced by CETP deficiency due to a CETP gene. Two common mutants of the CETP gene produce a CETP deficiency and resultant antiatherogenic lipoprotein pattern (i.e. hyper-HDL-cholesterolemia and hypo-LDL-cholesterolemia), and the frequency of the mutant allele is more than 1 in 10 subjects in Japan. Finally, we found unique patients with double heterozygotes of FH and CETP deficiency. We found 16 double heterozygotes of the LDL receptor gene and CETP gene. Four of the 16 patients showed myocardial infarction and 4 showed angina pectoris. These findings suggest that the atherogenicity of hyper-LDL-cholesterolemia in FH is more powerful than antiatherogenicity of hyper-HDL-cholesterolemia in CETP deficiency.
authors.affiliation: 2nd Department of Internal Medicine, Kanazawa University School of Medicine.
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D003327:Coronary Disease / Q000209:etiology*; D006023:Glycoproteins; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D011973:Receptors, LDL; D002784:Cholesterol