Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C →T mutation of low-density lipoprotein receptor gene  

作　　者：LIN Jie WANG Lu-ya LIU Shu XIA Jun-hui YONG Qiang DU Lan-ping PAN Xiao-dong XUE Hong CHEN Bao-sheng JIANG Zhi-sheng 

机构地区：[1]Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China [2]Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China [3]Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China

出　　处：《Chinese Medical Journal》2008年第9期776-781,共6页中华医学杂志（英文版）

基　　金：This study was supported by grants from the National Natural Science Foundation of China （No, 30470722, 30771982, 30772356）, Beijing Natural Science Foundation （No. 7052021, 7062010）, and Science and Technology New Star Funds of Beijing （No. 2004B27, 2005A29）

摘　　要：Background Familial hypercholesterolemia （FH）, caused by low density lipoprotein （LDL） receptor （LDL-R） gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation. Methods The patient＇s LDL-R gene coding region was sequenced. The patient＇s lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient＇s heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging （MPI）. Results The patient＇s LDL-R expression, LDL binding and up-take functions were significantly lower than normal control （39%, 63% and 76% respectively）. A novel homozygous 1439 C→T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes. Conclusions The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.Background Familial hypercholesterolemia （FH）, caused by low density lipoprotein （LDL） receptor （LDL-R） gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation. Methods The patient＇s LDL-R gene coding region was sequenced. The patient＇s lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient＇s heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging （MPI）. Results The patient＇s LDL-R expression, LDL binding and up-take functions were significantly lower than normal control （39%, 63% and 76% respectively）. A novel homozygous 1439 C→T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes. Conclusions The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.

关 键 词：familial hypercholesterolemia LDL receptor gene mutation gene function 

分 类 号：R54[医药卫生—心血管疾病]