Correlation of Lipoprotein Abnormalities in Childhood with the Risk for Atherosclerotic Coronary Heart Disease (CAD) in Adulthood (HDL function and polymorphism in HDL related genes)

1.小颗粒低密度脂蛋白(LDL)被认为比大颗粒低密度脂蛋白(LDL)更容易导致动脉粥样硬化，尽管这种联系可能取决于血浆甘油三酯(TG)和高密度脂蛋白(HDL)水平。为了帮助预防冠状动脉疾病(CAD)，了解儿童和青少年时期的危险因素可能是有用的。在本研究中，我们用梯度凝胶电泳法对70名健康儿童(30名男孩和40名女孩)的低密度脂蛋白颗粒大小(LDL-Size)以及被认为影响低密度脂蛋白大小的常规脂质和脂蛋白参数进行了评估。血浆和高密度脂蛋白中胆固醇的部分酯化速率和摩尔酯化速率(PER和MER)也如预期的那样被测定。无论男女，血浆TG、HDLC和apoA-I水平与低密度脂蛋白的大小密切相关。然而，在高密度脂蛋白中的FER(FERHDLE)和低密度脂蛋白的大小之间发现了更密切的联系。在逐步多元回归分析中，仅FERHDL76%，…男孩和女孩的低密度脂蛋白大小的变异性分别超过41%。高密度脂蛋白中的MER在男孩和女孩中分别占4%和19%。其他指标，包括血浆甘油三酯、高密度脂蛋白胆固醇和载脂蛋白A-I，没有显著的额外影响。因此，FERHDL值的测定有助于预测儿童低密度脂蛋白的颗粒大小。低血浆E{DL-C是成人冠心病的主要危险因素。在儿科领域，肥胖或血脂异常的儿童中经常会发现低密度脂蛋白胆固醇的受试者。本研究的目的是通过比较年龄匹配的正常高密度脂蛋白胆固醇儿童和低高密度脂蛋白胆固醇的冠心病患者的血脂和载脂蛋白水平以及他们的高密度脂蛋白的理化特征来评估低高密度脂蛋白胆固醇儿童的冠心病风险。为探讨高密度脂蛋白胆固醇(HDL40 mg/dL)的理化特性，测定128例HDLc正常儿童、71例血脂异常儿童、33例肥胖症儿童和93例CAD儿童的血浆胆固醇(高脂血浆和高铁血浆)和高密度脂蛋白(高密度脂蛋白和高密度脂蛋白)的摩尔和分数酯化率，并与正常儿童比较，发现低高密度脂蛋白胆固醇儿童的血脂和载脂蛋白水平及高密度脂蛋白的理化特征。接下来，我们研究了低HOL-C儿童和低高密度脂蛋白胆固醇的冠心病患者在血脂和载脂蛋白谱上的差异。30 mg/dL，II组30l-高密度脂蛋白胆固醇40mgdL)。与冠心病组相比，I组儿童动脉粥样硬化的载脂蛋白谱较少(apoB较低，apoA-I/apoB较高)。在第二组儿童中也发现了类似的发现，但差异没有第一组儿童那么显著。低高密度脂蛋白胆固醇儿童的FERHDL值与冠心病组相似。提示低高密度脂蛋白胆固醇组儿童HbL的理化特征与冠心病组相似，但载脂蛋白B的异常程度较冠心病组轻。因此，如果我们能够防止含有apoB的脂蛋白性质的进一步改变，低HDLc的儿童在以后的生活中可能不会成为冠心病的高风险。3.对D442G和Intl4A缺乏CETP的基因进行了PCR-RFLP分析，并从大规模筛查发现的血脂异常儿童的干燥血斑中提取DNA。由熊本大学医院的临床营养师进行营养分析。对181例血脂异常儿童进行CETP基因分析。未发现Intl4A携带者，但发现13例D442G杂合子。其血浆高密度脂蛋白-C、载脂蛋白A-I、载脂蛋白A-II水平与无CETP基因突变的儿童相似。这些结果表明，幼儿CETP缺乏可能不影响血浆高密度脂蛋白水平，可能需要其他因素来提高血浆高密度脂蛋白水平。较少

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