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Familial hypercholesterolemia (FH) is one of the most common primary hyperlipidemias, characterized by a heterozygous or homozygous phenotype for a severe serum low-density lipoprotein (LDL)-cholesterol level and advanced atherosclerosis, leading to coronary artery diseases (CAD). Various kinds of mutations in the LDL receptor gene responsible for the genetic disease have been identified since the human LDL receptor gene has been identified. In this study, the clinical features of FH were investigated using a database based on nationwide surveillance for primary hyperlipidemia and related disorders by the Research Committee on Primary Hyperlipidemia. The clinical features and the frequencies of accompanying vascular diseases in 660 cases of FH homozygotes and heterozygotes showed that the incidence of CAD was negatively associated with plasma HDL-cholesterol levels, but not with plasma LDL-cholesterol levels, in 641 FH heterozygotes. Risk factor analyses revealed that hypertension, male, smoking, low HDL-cholesterol levels, age &gt; 50 y, diabetes mellitus, and hypertriglyceridemia were positive risk factors for CAD. The summarized gene analysis in FH heterozygotes showed at least 4 mutations in the LDL receptor gene as common mutations in Japan. The average serum lipids and frequency of CAD based on each common mutation suggested that their clinical features are in part determined by responsive mutations in the LDL receptor gene.

journal of atherosclerosis and thrombosis

Clinical Features of Familial Hypercholesterolemia in Japan in a Database from 1996&amp;minus;1998 by the Research Committee of the Ministry of Health, Labour and Welfare of Japan