Genetic cholesteryl ester transfer protein deficiency is extremely frequent in the Omagari area of Japan - Marked hyperalphalipoproteinemia caused by CETP gene mutation is not associated with longevity
Genetic cholesteryl ester transfer protein deficiency is extremely frequent in the Omagari area of Japan - Marked hyperalphalipoproteinemia caused by CETP gene mutation is not associated with longevity
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DOI：
10.1161/01.atv.17.6.1053
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发表时间：
1997-06-01
影响因子：
8.7
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Hirano, K;Yamashita, S;Matsuzawa, Y
低水平的高密度脂蛋白胆固醇已被明确地证明与冠心病发病率的增加有关，这强烈地表明高密度脂蛋白颗粒具有抗动脉粥样硬化的功能。然而，关于一种显著的高脂蛋白血症(一半)的致动脉粥样硬化作用的信息很少。关于血浆胆固醇酯转移蛋白(CETP)缺乏是否与抗动脉粥样硬化状态相关，目前尚无一致意见，尽管这种疾病被报道为明显一半的主要原因之一。在目前的研究中，我们发现了一个独特的地区(日本秋田县大沼市)，CETP基因内含子14的5‘剪接供体位点G-to-A突变引起的CETP缺乏症非常频繁。在奥马加里市，检测到这种突变的频率是日本其他地区的20多倍，血浆高密度脂蛋白胆固醇大于或等于2.58 mmol/L(100 mg/dL)的显著一半的患病率是日本其他地区的5到10倍。这一发现使得进行一项大规模的基于人群的研究成为可能，该研究涉及在遗传更均匀的人群中高密度脂蛋白胆固醇显著升高的致动脉粥样硬化作用。在心电图中，高密度脂蛋白胆固醇水平和缺血性改变的发生率之间存在显著的统计学意义的U型关系。在高密度脂蛋白胆固醇80岁的病例中，显著的HALP和内含子14剪接缺陷的患病率显著低于年轻一代。目前的研究首次表明，CETP基因突变引起的显著HALP可能不代表长寿综合征，这表明重新评估显著HALP的临床意义和病理生理学的重要性。
Low levels of HDL cholesterol have been clearly demonstrated to be associated with an increased incidence of coronary heart disease, strongly suggesting that HDL particles have an antiatherogenic function. However, little information has been available concerning the atherogenicity of a marked hyperalphalipoproteinemia (HALF). There is no agreement about whether plasma cholesteryl ester transfer protein (CETP) deficiency is associated with an antiatherogenic state or not, although this disorder was reported to be one of the major causes of marked HALF. In the current study, we have found a unique area (Omagari City, Akita Prefecture, Japan) where CETP deficiency caused by a G-to-A mutation at the 5' splice donor site of intron 14 in the CETP gene is extremely frequent. In Omagari City, the mutation was detected more than 20 times more frequently and the prevalence of a marked HALF with plasma HDL cholesterol greater than or equal to 2.58 mmol/L (100 mg/dL) was 5 to 10 times higher than in other areas of Japan. This discovery has made it possible to perform a large population-based study concerning the atherogenicity of a marked elevation of HDL cholesterol in a genetically more homogeneous population. There was a statistically significant U-shaped relationship between HDL cholesterol levels and the incidence of ischemic changes in electrocardiograms. In cases of HDL cholesterol 80 years, the prevalence of both marked HALP and the intron 14 splicing defect was significantly lower than in the younger generation. The current study indicated for the first time that a marked HALP caused by CETP gene mutation may not represent a longevity syndrome, suggesting the importance of reevaluation of the clinical significance and pathophysiology of a marked HALP.