Quantity, function and genetics of HDL as an indicator of CHD.

HDL 的数量、功能和遗传学作为 CHD 的指标。

• 批准号: 07670827
• 负责人: SAKU Keijiro
• 金额: $ 1.34万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670827/
• 关键词: apolipoprotein A-I; atherosclerosis; coronary angiography; FER_<HDL>; HDL-C; Gene; polymorphism; 虚血性心臓病

Study 1 : Quantity and Function of High Density Lipoprotein as an Indicator of CoronaryAtherosclerosis Background Most of the cholesterol esterification in plasma takes place in the high density lipoprotein (HDL) fraction. The rate of cholesterol esterification in low density (LDL)-and very low density lipoprotein (VLDL)-depleted plasma, which can be expressed as the fractional esterification rate in HDL (FER_<HDL>), and which reflects the reactivity of HDL to lecithin : cholesterol acyltransferase (LCAT), is an important functional assay of HDL.The aim of the present study was to investigate the role of this functional assay of HDL in coronary atheroscierosis (CA) and to establish the best indicator for CA through the combination of quantitative and functional assays of HDL while considering conventional risk factors. Mehods and Results in a study of case and control subjects [with (CA+, n=185)/without (CA-, n=74) angiographically proven CA], we examined the association between CA and … More serum levels of HDL-cholesterol (C), HDL subfraction-C,apolipoproteins, lipoprotein (a), and FER_<HDL>. Age-and sex-adjusted values of HDL-C,HLD2-C,HLD3-C,apo A-I,and apo A-II were lower and those of lipoprotein (a) and FER_<HDL> were higher in CA+ patints than in CA-patients, but these variables were not associated with the extent of stenosis. A close negative correlation was observed between FER_<HDL> and HDL-C in both CA+ and CA- patients, but a covariance analysis indicated significant interaction between the regression line of FER_<HDL> vs. HDL-C for CA+ patients and that for CA-oatients, suggesting an altered relationship between the quantity and function of HDL in CA+ patients. A logistic regression analysis indicated that an increased odds ratio (relative risk for CA) was associated with increasing values of FER_<HDL>/HDL-C.A three-dimensional analysis of the odds ratio and values of FER_<HDL> and HDL-C indicated that patients with the highest FER_<HDL>/HDL-C value (0.68) had the highest odds ratio (12.6), but patients who had the lowest odds ratio (1.00) were those with high HDL-C and high FER_<HDL> values. The odds ratio was>10 times higher in patients with low HDL-C and middle or high FER_<HDL> values and 2.3 times higher in patients with low HDL-C and low FER_<HDL> values than in patients with high HDL-C and FER_<HDL> values, which suggests that high values of FER_<HDL> play an important role in CA,especially when HDL-C is low. Conclusion The combination of a functional assay of HDL (FER_<HDL>) with a quantitative assay of HDL (HDL-C) can be a potent indicator for caronary atherosclerosis. Less

研究1：高密度脂蛋白作为冠状动脉粥样硬化指标的含量和功能研究背景血浆中大部分胆固醇的酯化作用发生在高密度脂蛋白（HDL）组分中。在低密度（LDL）和极低密度脂蛋白（VLDL）耗尽的血浆中胆固醇酯化的速率，其可以表示为HDL中的酯化率分数（FER_<HDL>），并且其反映HDL对卵磷脂的反应性：胆固醇酰基转移酶（LCAT），是一种重要的HDL功能测定方法，本研究旨在探讨HDL功能测定在冠状动脉粥样硬化（CA）中的作用并结合HDL的定量和功能检测，结合传统的危险因素，建立CA的最佳指标。方法和结果在一项病例和对照组[有（CA+，n=185）/无（CA-，n=74）血管造影证实的CA]的研究中，我们检查了CA和 ...更多信息 HDL-胆固醇（C）、HDL亚组分-C、载脂蛋白、脂蛋白（a）和FER_1的血清水平<HDL>。CA+患者HDL-C、HLD_2-C、HLD_3-C、apoA-I、apoA-II的性别校正值低于CA-患者，而Lp（a）、FER_2的性别校正值<HDL>高于CA-患者，但这些变量与狭窄程度无关。CA<HDL>+和CA-患者的FER_2与HDL-C均呈负相关，但协方差分析表明CA+患者的FER_2与HDL-C的回归线与CA-患者的回归线之间存在显著的交互作用<HDL>，提示CA+患者HDL的数量与功能之间的关系发生了改变。Logistic回归分析显示，FER_/HDL-C值升高与CA的相对危险度（OR）增加有关<HDL>。三维分析<HDL>显示，FER_/HDL-C值最高<HDL>（0.68）的患者OR最高（12.6），而OR最低（1.00）的患者为高HDL-C和高FER_值的患者<HDL>。低HDL-C、中、高FER_2患者的OR值比高HDL-C、高FER_2患者高10倍<HDL>以上，低HDL-C、低FER_<HDL>2患者的OR值比高HDL-C、高<HDL>FER_2患者高2.3倍，提示高FER<HDL>_2在CA发病中起重要作用，尤其是HDL-C低时。结论高密度脂蛋白功能测定（FER_<HDL>）和高密度脂蛋白定量测定（HDL-C）相结合可作为冠状动脉粥样硬化的有效指标。少

项目成果

Takata K., Saku K., Ohta T., Takata M., Bai H., Jimi S., Liu R., Sato H., Kajiyama G., Arakawa K.: "A new case of apo A-I deficiency showing codon 8 nonsense mutation of the apo A-I gene without evidence of coronary heart disease." Arterioscle Thromb Vasc

Takata K.、Saku K.、Ohta T.、Takata M.、Bai H.、Jimi S.、Liu R.、Sato H.、Kajiyama G.、Arakawa K.：“显示密码子的 apo A-I 缺陷的新病例

Yamada K., Ideishi M., Nii T., Shirai K., Noguchi H., Murakami K., Noda Y., Matsuo K., Handa K,.Okabe M., Saku K., Kawaguchi H., Tanaka K., Arakawa K.: "An analysis of the patients presenting with acute myocardial infarction during a one-year period of 19

山田 K.、出井石 M.、新井 T.、白井 K.、野口 H.、村上 K.、野田 Y.、松尾 K.、半田 K、冈部 M.、佐久 K.、川口 H.、田中 K

Saku K., Zhang B., Arakawa K.: "Troglitazone lowers blood pressure and enhances insulin sensitivity in Watanabe heritable hyperlipidemic rabbits." Am J Hypertension. (in press). (1997)

Saku K.、Zhang B.、Arakawa K.：“曲格列酮可降低渡边遗传性高脂血症兔子的血压并增强胰岛素敏感性。”

Bai H.,Saku et al: "Polymorphism of the apolipoprotein A-IV gene and its significance in lipid metabolism and coroanry heart disease in a Japanese population." Europ J Clin Invest.26. 1115-1124 (1996)

Bai H.，Saku 等人：“载脂蛋白 A-IV 基因的多态性及其在日本人群脂质代谢和冠心病中的意义。”

Muntoni S.,Saku K.,et al: "A missense mulation (Thr-BPro) in the lysosomal acid Npase (LAL) gene is present with a high frequency in three different ethnlc populations : lmpact on serum Npoprolein concantrations." Human Genetics. 97. 265-267 (1996)

Muntoni S.、Saku K. 等人：“溶酶体酸性 Npase (LAL) 基因中的错义结构 (Thr-BPro) 在三个不同种族人群中出现频率较高：对血清 Npoprolein 浓度有影响。”