| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Research Abstract |
1. Small low density lipoprotein (LDL) particles are thought to be more atherogenic than larger LDL particles, although this association may depend on plasma triglyceride (TG) and high density lipoprotein (HDL) levels. To help prevent coronary artery disease (CAD), it may be useful to understand risk factors during childhood and adolescence. In the present study, we evaluated low density lipoprotein particle size (LDL-size) by gradient gel electrophoresis in 70 healthy children (30 boys and 40 girls) along with conventional lipid and lipoprotein parameters which are thought to affect LDL-size. The fractional and molar esterification rates (PER and MER) of cholesterol in plasma and HDL were also determined As expected, plasma levels of TG, HDL-cholesterol (HDL-C) and apoA-I were closely associated with LDL-sizes in both sexes. However, a closer association was found between FER in HDL (FERHDL) and LDL-size. In a stepwise multiple regression analysis, FERHDL alone accounted for 76 % and
… More
41 % of the variability in LDL-size in boys and girls, respectively. MER in HDL accounted for additional 4 % and 19 % in boys and girls, respectively. Other parameters, including plasma TG, HDL-C and apoA-I had no significant additional effects. Thus, the determination of FERHDL is useful to predict the particle size of LDL in children.
2. Low plasma E{DL-C is a major risk factor for CAD in adults. In the field of pediatrics, subjects with low plasma HDL-C are often found among obese or dyslipidemic children. However, it is not clear whether low HDL-C in children should be considered a risk factor for CAD.The purpose of this study was to evaluate the risk for CAD in children with low HDL-C by comparing their lipid and apolipoprotein levels and physicochemical characteristics of their HDL with those of age-matched children with normal HDL-C and CAD patients with low HDL-C.Plasma lipids and apolipoproteins were measured in 206 dyslipidemic children (dyslipidemic), 65 obese children (obese), 93 CAD patients with low HDL-C (<40 mg/dL) and 128 children with normal HDL-C.To evaluate the physicochemical characteristics of HDL, molar and fractional esterification rates of cholesterol in plasma (MERplasma and FERplasma) and HDL (MERHDL and FERHDL) were determined in 128 children with normal HDL-C, 71 dyslipidemic, 33 obese and 93 CAD.Compared with controls, children with low HDL-C showed atherogenic profiles of lipid and apolipoprotein levels and physicochemical characteristics of HDL.Therefore, we next examined the differences in lipid and apolipoprotein profiles between children with low HOL-C and CAD patients with low HDL-C.We studied two groups of subjects based on the HDL-C level (Group I : <30 mg/dL, Group II 30l-HDL-C<40mgldL). Compared with CAD, Group I children showed less atherogenic apolipoprotein profiles (lower apoB and higher ratio of apoA-I to apoB). Similar findings were also found in Group II children, but the differences were less prominent than those in Group I children. FERHDL in children with low HDL-C were similar to those in CAD.These findings suggest that the physicochemical characteristics of HbL in children with low HDL-C are similar to those in CAD, but the abnormalities of apoB-containing lipoproteins are milder than those in CAD patients. Thus, if we could prevent further changes in the nature of apoB-containing lipoproteins, children with low HDL-C might not become high risk for CAD in later life.
3.Gene analysis for CETP deficiency was carried out by PCR-RFLP for D442G and Intl4A.DNA was extracted from dried blood spots from dyslipidernic children detected by mass screening. Nutritional analysis was performed by clinical dietitian in Kumamoto University hospital. Gene analysis for CETP was done in 181 dyslipidemic children. Children with Intl4A was not found However, we could find 13 children with heterozygote for D442G mutation. Their plasma levels of HDL-C, apoA-I and apoA-II were similar to those in children with no mutations of CETP gene. These results indicate that CETP deficiency in young children may not affect the plasma concentrations of HDL.Other factor might be required to raise the plasma levels of HDL. Less
|
