| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Cholesteryl ester transfer protein (CETP) can transfer cholesteryl ester from high density lipoprotein to apoB-containing lipoproteins. Our first report of familial CETP deficiency in 1980, revealed that the deficiency of CETP caused extremely high HDL cholesterol levels. Therefore, CETP plays an important role in HDL cholesterol metabolism. The CETP deficiency is caused by the mutation of intron 14 splice donor site of CETP gene, and the mutation of the CETP gene is common in CETP deficiency, resulted from the study of haplotype analysis.
In this study, we developed a new methods about detecting the intron 14 splicing defect in CETP deficiency, and have searched the heterozygote of CETP deficiency. Allele frequency of the mutation was 8.0 % and 52.4 % in the groups of 100-119 mg/dl and equal or exceeded 120 mg/dl of HDL cholesterol. In the group of equal or exceeded 120 mg/dl of HDL cholesterol, 14 patients i 21 had the mutation of CETP gene, but other 7 patients had not. There was an increase of cholesteryl ester/triglyceride ratio in HDL in the heterozygous patients with CETP deficiency. Serum CETP concentration positively related to the intermediate density lipoprotein (IDL) cholesteryl ester and cholesteryl ester/triglyceride ratio. Thus, since the IDL cholesterol is atherogenic, the reduced IDL cholesterol in the heterozygotes may be anti-atherogenic.
In conclusion, there was an anti-atherogenic change in the lipoprotein pattern in plasma obtained from the heterozygous patients with CETP deficiency. The frequency of coronary atherosclerosis in the heterozygotes should be studied in the near future.
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