Mutations in Japanese subjects with primary hyperlipidemia--results from the Research Committee of the Ministry of Health and Welfare of Japan since 1996--.

Primary hyperlipidemia is caused by various molecular defects in lipid metabolism. The Research Committee on Primary Hyperlipidemia organized by the Ministry of Health and Welfare of Japan (present: the Ministry of Health, Labour and Welfare) has investigated reported mutations in Japanese patients with primary hyperlipidemia and related disorders (including hypolipidemia), and has created a database based on the questionnaire sent to the members of council board of the Japan Atherosclerosis Society. Mutations in the following genes were investigated: low density lipoprotein receptor, lecithin: cholesteryl acyltransferase, lipoprotein lipase (LPL), hepatic lipase, apolipoproteins A-I, A-II, A-IV, B, C-II, C-III and E, microsomal triglyceride transfer protein, and cholesterol ester transfer protein (CETP). Until 1998, 922 patients with primary hyperlipidemia and related disorders has been registered with the Research Committee, and 190 mutations in 15 genes had been reported, showing a marked variation in Japanese patients with primary hyperlipidemia and related disorders. So-called "common mutations" have been described in Japanese patients with familial hypercholesterolemia, LPL deficiency and CETP deficiency. The genetic defect of familial combined hyperlipidemia (FCHL) is still unknown although FCHL is speculated to be the most prevalent genetic hyperlipidemia, and further investigations should be performed to elucidate the molecular mechanisms of FCHL