卵磷脂:胆固醇酰基转移酶(lecithin:cholesterol acyltransferase,LCAT)参与胆固醇酯的合成并在高密度脂蛋白(high density lipoprotein,HDL)的代谢中起重要作用。遗传性LCAT缺陷症是一种以低HDL-胆固醇(HDL-C)为特点的罕见遗传疾病。...卵磷脂:胆固醇酰基转移酶(lecithin:cholesterol acyltransferase,LCAT)参与胆固醇酯的合成并在高密度脂蛋白(high density lipoprotein,HDL)的代谢中起重要作用。遗传性LCAT缺陷症是一种以低HDL-胆固醇(HDL-C)为特点的罕见遗传疾病。近年来,LCAT在HDL-C代谢中以及在动脉粥样硬化发生和发展中的作用逐渐被本领域研究者所关注。本文就LCAT缺陷症的遗传学和生化学特点做一综述,重点阐述为何尽管HDL-C水平明显减低,LCAT突变携带者却并未发生早期动脉粥样硬化。展开更多
Background-Prospective epidemiological studies have shown that low plasma levels of HDL cholesterol(HDL-C) are associated with an increased risk for cardiovascular disease(CVD). Despite nearly 40 years of research, ho...Background-Prospective epidemiological studies have shown that low plasma levels of HDL cholesterol(HDL-C) are associated with an increased risk for cardiovascular disease(CVD). Despite nearly 40 years of research, however, it is unclear whether this also holds true for individuals with severely reduced levels of HDL-C due to mutations in the lecithin: cholesterol acyltransferase(LCAT) gene. Better insight into CVD risk in these individuals may provide clues toward the potential of LCAT as a pharmaceutical target to raise HDL-C levels. Methods and Results-Lipids, lipoproteins, high-sensitivity C-reactive protein(CRP), and carotid artery intima-media thickness(IMT) were assessed in 47 heterozygotes for LCAT gene mutations and 58 family controls. Compared with controls, heterozygotes presented with a mean 36%decrease in HDL-C levels(P< 0.0001), a 23%increase in triglyceride levels(P< 0.0001), and a 2.1-fold increase in CRP levels(P< 0.0001). Mean carotid IMT was significantly increased in heterozygotes compared with family controls(0.623±0.13 versus 0.591±0.08 mm). After adjustment for age, gender, and alcohol use, this difference proved statistically significant(P< 0.0015). Conclusions-The data show that heterozygosity for LCAT gene defects is associated with low HDL-C levels and elevated concentration of triglycerides and CRP in plasma. This phenotype underlies increased IMT in carriers versus controls, which suggests that LCAT protects against atherosclerosis. This in turn indicates that targeting LCAT to raise HDL-C may reduce CVD risk.展开更多
文摘卵磷脂:胆固醇酰基转移酶(lecithin:cholesterol acyltransferase,LCAT)参与胆固醇酯的合成并在高密度脂蛋白(high density lipoprotein,HDL)的代谢中起重要作用。遗传性LCAT缺陷症是一种以低HDL-胆固醇(HDL-C)为特点的罕见遗传疾病。近年来,LCAT在HDL-C代谢中以及在动脉粥样硬化发生和发展中的作用逐渐被本领域研究者所关注。本文就LCAT缺陷症的遗传学和生化学特点做一综述,重点阐述为何尽管HDL-C水平明显减低,LCAT突变携带者却并未发生早期动脉粥样硬化。
文摘Background-Prospective epidemiological studies have shown that low plasma levels of HDL cholesterol(HDL-C) are associated with an increased risk for cardiovascular disease(CVD). Despite nearly 40 years of research, however, it is unclear whether this also holds true for individuals with severely reduced levels of HDL-C due to mutations in the lecithin: cholesterol acyltransferase(LCAT) gene. Better insight into CVD risk in these individuals may provide clues toward the potential of LCAT as a pharmaceutical target to raise HDL-C levels. Methods and Results-Lipids, lipoproteins, high-sensitivity C-reactive protein(CRP), and carotid artery intima-media thickness(IMT) were assessed in 47 heterozygotes for LCAT gene mutations and 58 family controls. Compared with controls, heterozygotes presented with a mean 36%decrease in HDL-C levels(P< 0.0001), a 23%increase in triglyceride levels(P< 0.0001), and a 2.1-fold increase in CRP levels(P< 0.0001). Mean carotid IMT was significantly increased in heterozygotes compared with family controls(0.623±0.13 versus 0.591±0.08 mm). After adjustment for age, gender, and alcohol use, this difference proved statistically significant(P< 0.0015). Conclusions-The data show that heterozygosity for LCAT gene defects is associated with low HDL-C levels and elevated concentration of triglycerides and CRP in plasma. This phenotype underlies increased IMT in carriers versus controls, which suggests that LCAT protects against atherosclerosis. This in turn indicates that targeting LCAT to raise HDL-C may reduce CVD risk.
