| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Cholesteryl ester transfer protein (CETP) mediates the heteroexchange of HDL cholesteryl esters with triglycerides of VLDL and chylomicrons. The impaired triglyceride-rich lipoprotein metabolism and accumulaton of remnant lipoproteins, has been reported in diabetic or familial combined hyperlipidemic patiens. The increased CETP activity may produce atherogenic lipid compositions of apoprotein-B-containing lipoproteins, as a result of cholesterol transport from HDL.To study a role of CETP in the impaired remnant metabolism, the CETP gene mutations were searched in Japanese people, and the insulin resposes after glucose administration in FCHL patients were examined.
Two novel mutations were identified : an intron 14 splice donor site mutation caused by a T insertion at position +3 (Int14 T) and a missense mutation (Asp442 to Gly) within exon 15 (D442G), in addition to an intron 14G (+1) to A mutaion (Int14 A) which was previously reported. Prevalences of the D442G and Int14 A mutations were extremely high in the general sample of Japanese men (n=236), with heterozygote frequencies of 7% and 2%, respectively.
According to the 75gOGTT,35% of FCHL patients showed an impaired glucose tolerance and 25% of FCHL patients a diabetic glucose tolerance. Area under the plasma insulin concentration-time curve in the FCHL patients with normal and impaired glucose tolerances were significant higher than those in the control group (p<0.05). There were significant relationships between AUC-IRI and LDL-cholesterol levels (p<0.05). FCHL and hyperinsulinemia in diabetic patients, may be important factors linkaging diabetes and CHD.
In conclusion, FCHL patients showed hyperinsulinemia after glucose administration, and may contribute to the increased CHD in the patients with glucose intolerance. CETP may play a role in the impaired remnant metabolism in FCHL and diabetic patients. Further study will be required.
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