Relationship between lipoprotein abnormalities in childhood and the risk for atherosclerotic coronary heart disease in adulthood(Comparison of the effects of genetic and environmental factors on dyslipidemia between children and adults)

儿童期脂蛋白异常与成年后动脉粥样硬化性冠心病风险的关系（遗传因素和环境因素对儿童与成人血脂异常的影响比较）

基本信息

批准号：
13470166
负责人：
OHTA Takao
金额：
$ 8.96万
依托单位：
University of the Ryukyus
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

1.Acyl-CoA : cholesterol acyltransferase(ACAT)plays important roles in cellular cholesterol homeostasis.Two isoforms of ACAT have been reported(ACAT-1 and ACAT-2).An ACAT inhibitor was shown to have a lipid-lowering effect.The present study was carried out to clarify the relationship between ACAT-1 gene variants and hyperlipidemia.A missense variant(R526G), and a variant in the 5' untranslated region(-77G-.A) were identified.R526G variant did not affect plasma concentrations of lipids or apolipoproteins in subjects studied. However, among hyperlipidemic subjects, plasma concentrations of HDL-C and apoA-I in subjects with -77G-'A variant were significantly higher than those in subjects without variant.These data suggest that the intracellular PC concentration might modulate plasma HDL concentrations.2.Small LDL particles are more atherogenic than larger LDL particles.To help prevent atherosclerotic coronary heart diseases(ACHD), it may be useful to understand risk factors during childhood. We evaluated LDL-size and its relation tQ other risk factors for ACHD.LDL-size was measured by gradient gel electrophoresis in 586 children.Pattern B(LDL-size < 25.5 nm)was found in 10.8 % of boys and 4.4 % of girls.Children with pattern B had a higher body mass index (BMI) and insulin resistance, and a more atherogenic lipoprotein profile than those with pattern A (LDL-size> 25.5 nm).BMI, insulin resistance and plasma concentrations of TG, glucose and insulin decreased and plasma concentrations of HDL-C and apoA-I increased as LDL-size increased.HDL-C and insulin in boys, and BMI, HDL-C and apoA-I in girls predicted 22.9 % and 28.1 % of the variability of LDL-size, respectively.Although the contribution Qf these parameters to LDL-size in children was less than that in adults, improvement of these parameters by changes in lifestyle might be important for preventing the development of atherosclerosis, even in children.

1.1.ACYL-COA：胆固醇酰基转移酶（ACAT）在细胞胆固醇稳态中起重要作用。已经报道了ACAT的两种同工型（ACAT-1和ACAT-2）。ACAT抑制剂显示出具有脂脂型效应的ACAT抑制剂。目前的研究效果已阐明了ACAT-1 Gene Veriant and Acat-1 Miveseraim nifferaia。鉴定了5'非翻译区域（-77G -.A）中的变体（R526G）和变体。R526G变体不影响所研究受试者中脂质或载脂蛋白的血浆浓度。然而，在高脂受试者中，-77G-'A变体的受试者中的HDL-C和APOA-I的血浆浓度明显高于没有变体的受试者中的HDL-C和APOA-I。这些数据表明，这些细胞内PC浓度可能调节血浆HDL浓度。2.SmallLDL颗粒比更大的LDL颗粒相比，可以防止更大的LDL颗粒。有助于一个较大的ldl颗粒。疾病（ACHD），在儿童期了解危险因素可能很有用。我们评估了LDL大小及其关系TQ aChd.ldl-size的其他风险因素是通过586名儿童的梯度凝胶电泳来测量的。在10.8％的男孩和4.4％的女孩中，Pattern B（LDL-Size <25.5 nm）在具有图案的Girls.4.4％的男孩中。（LDL-Size> 25.5 nm）.BMI，Tg，葡萄糖和胰岛素的胰岛素抵抗和血浆浓度降低，HDL-C和APOA-I的血浆浓度随着LDL-Size的增加而增加。HDL-C和BMI，HDL-C和HDL-C和APOA-I的HHDL-C和胰岛素的变化。尽管QF的贡献分别为儿童中的LDL大小的贡献少于成年人，但通过生活方式的改变来改善这些参数可能对于防止动脉粥样硬化的发展也很重要，即使在儿童中也是如此。