Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2005, Vol. 3 ›› Issue (6): 438-442.doi: 10.3736/jcim20050605

• Original Clinical Research • Previous Articles     Next Articles

Study on relationship between polymorphism of apolipoprotein E gene and syndromes of phlegm and blood stasis in patients with coronary heart disease

Tao Ouyang1,2, Jian-nan Song1, Yang Miao3, Qian Lin4, Xiao-hong Niu1, Hong Jin1, Bing Chen1   

  1. 1. Department of Biochemistry, Institute of Basic Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, China
    2. Department of Immunology, Beijing Institute of Geriatrics, Ministry of Public Health, Beijing 100730, China
    3. Department of Cardiology, Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing 100091, China
    4. Department of Cardiology, Dongfang Hospital, Beijing University of Traditional Chinese Medicine, Beijing 100078, China
  • Online:2005-11-20 Published:2005-11-20
  • Contact: Jian-nan Song


To explore the relationship between polymorphism of apolipoprotein E (ApoE) exon 4 gene and different syndromes in patients with coronary heart disease (CHD).


Two hundred patients with CHD were divided into four groups according to syndrome differentiation, including syndrome of phlegm (PS), syndrome of blood stasis (BSS), syndrome of phlegm-blood stasis blocking (PBBS) and syndrome of non-phlegm and non-blood stasis (NPNBS). One hundred healthy volunteers were included in control group. Blood lipids were measured by routine examination. Total DNA of peripheral blood was extracted. ApoE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. All data were analyzed by SAS software.


(1) The occurrence rate of ε4 allele of ApoE in patients with CHD was 19.5%, significantly higher than 9.5% in the control group (P<0.05), and the E 3/4 genotype was especially more frequent (P<0.01). (2) The levels of total cholesterol (TC), total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in patients with ε4 were higher than those in patients without ε4 (P<0.01). (3) The frequencies of ε4 allele and E3/4 genotype in patients with PS were significantly higher than those in patients with BSS (P<0.05).


ApoE ε4 allele, especially E3/4 genotype, is the risk factor of CHD. There is a relatively close relationship between patients with ApoE ε4 allele and PS. It may be one of the main susceptible genes in CHD patients with PS.

Key words: Coronary heart disease, Apolipoprotein E, Gene polymorphism, Syndrome of phlegm and blood stasis

CLC Number: 

  • R2-03

Fig 1

PCR amplification results of ApoEexon 4 target fragment M: PCR marker; 1: PCR products; 2: PCR products"

Fig 2

HhaI RFLP results of ApoE exon 4 PCR products M: pBR322-Hae Ⅲ marker; 1: Genotype E 3/3; 2: Genotype E 2/3; 3: Genotype E 2/4; 4: Genotype E 2/2; 5: Genotype E 3/4; 6: Genotype E 4/4"

Fig 3

Sequence mapping of genotype E 4/4 of ApoE "

Tab 1

Frequency distribution of ApoE exon 4 genotypes and alleles in CHD group and control group"

Group n Genotype frequency [% (cases)] Allele frequency [% (cases)]
E 3/3 E 4/4 E 3/4 E 2/3 E 2/2 E 2/4 ε2 ε3 ε4
Control 100 66.0 (66) 2.0 (2) 14.0 (14) 17.0 (17) 0 (0) 1.0 (1) 9.0 (18) 81.5(163) 9.5 (19)
CHD 200 49.0 (98)** 2.5 (5) 33.5 (67)** 14.0 (28) 0.5 (1) 0.5 (1) 7.7 (31) 72.8 (291) 19.5 (78)*

Tab 2

Comparison of serum lipid level between patients in CHD group with and without ε4 allele ($\bar{x}$±s )"

Group n TC (mmol/L) TG (mmol/L) HDL-C (mmol/L) LDL-C (mmol/L) AI
E 2/2+E 2/3+E 3/3 127 4.18±1.13 1.53±1.05 1.16±0.46 2.36±0.93 2.40±1.38
E 2/4+E 3/4+E 4/4 73 4.98±1.25** 2.17±2.45* 1.09±0.42 2.90±1.00** 3.00±1.53**

Tab 3

Frequency distribution of apoE exon 4 genotypes and alleles in CHD patients with different syndromes"

Group n Genotype frequency [% (cases)] Allele frequency [% (cases)]
E 3/3 E 4/4 E 3/4 E 2/3 E 2/2 E 2/4 ε2 ε3 ε4
PS 20 30.00(6) 5.00(1) 55.00(11) 10.00(2) 0(0) 0(0) 5.00(2) 62.50(25) 32.50(13)
BSS 79 58.23(46) 1.27(1) 25.32(20) 13.92(11) 0(0) 1.27(1) 7.59(12) 77.85(123) 14.57(23)
PBBS 82 48.78(40) 3.66(3) 30.49(25) 15.85(13) 1.22(1) 0(0) 9.14(15) 71.95(118) 18.91(31)
NPNBS 19 31.58(6) 0(0) 57.89(11)* 10.53(2) 0(0) 0(0) 5.26(2) 65.79(25) 28.95(11)
[1] Luthra K, Bharghav B, Chabbra S , et al. Apolipoprotein E polymorphism in Northern Indian patients with coronary heart disease: phenotype distribution and relation to serum lipids and lipoproteins[J]. Mol Cell Biochem, 2002,232(1-2):97-102
doi: 10.1023/A:1014869827322
[2] Ranjith N, Pegoraro RJ, Rom L , et al. Lp(a) and apoE polymorphisms in young South African Indians with myocardial infarction[J]. Cardiovasc J S Afr, 2004,15(3):111-117
[3] Peng DQ, Zhao SP, Nie S , et al. Gene-gene interaction of PPAR gamma and ApoE affects coronary heart disease risk[J]. Int J Cardiol, 2003,92(2-3):257-263
doi: 10.1016/S0167-5273(03)00101-3
[4] 丁邦晗, 马长生, 张敏洲 , 等. 胸痹心痛患者375例的冠脉病变程度及证型分析[J]. 中医药学刊, 2004,22(6):1096-1097, 1104
[5] 陈国伟, 郑宗锷 . 现代心脏内科学(第1版)[M]. 长沙: 湖南科学技术出版社, 2002,( 第1版):1051-1053
[6] Richard P , Thomas G, de Zulueta MP, et al.Common and rare genotypes of human apolipoprotein E determined by specific restriction profiles of polymerase chain reaction-amplified DNA[J]. Clin Chem, 1994,40(1):24-29
[7] Wetterau JR, Aggerbeck LP, Rall SC Jr , et al. Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains[J]. J Biol Chem, 1988,263(13):6240-6248
[8] 王克勤 . 脂蛋白与动脉粥样硬化(第1版)[M]. 北京: 人民卫生出版社, 1995,( 第1版):153-154
[9] Keavney B, Palmer A, Parish S , et al. Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls: discrepancies between genotype, blood lipid concentrations, and coronary disease risk[J]. Int J Epidemiol, 2004,33(5):1002-1013
doi: 10.1093/ije/dyh275
[10] Song Y, Stampfer MJ, Liu S . Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease[J]. Ann Intern Med, 2004,141(2):137-147
doi: 10.7326/0003-4819-141-2-200407200-00013
[11] 王阶, 李建生, 姚魁武 , 等. 血瘀证量化诊断及病证结合研究[J]. 中西医结合学报, 2003,1(1):21-24
[12] Zhang M . A study on relationship between balance of serum lipoprotein and the phlegm damp-blood stasis syndrome differentiation of coronary heart disease[J]. Medicine, 1995,15(3):9-12
[13] 宋剑南, 刘东远, 李爱华 , 等. 脑血康的化瘀祛痰功能与抗脂质过氧化物作用的关系[J]. 中国医药学报, 1993,8(增刊):47-49
[14] 宋剑南, 陈杲 . 论载脂蛋白E及其基因多态性与中医痰瘀证候的关系[J]. 中国中医基础医学杂志, 2002,8(12):13-15
[1] Yan-jun Lin, Kun-li Jiao, Bo Liu, Lu Fang, Shu Meng. Antiplatelet and myocardial protective effect of shexiang tongxin dropping pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial. Journal of Integrative Medicine, 2022, 20(2): 126-134.
[2] Mei-jiao Mao, Jun-ping Hu, Cong Wang, Yi-yi Zhang, Ping Liu. Effects of Chinese herbal medicine Guanxinkang on expression of PPARγ-LXRα-ABCA1 pathway in ApoE-knockout mice with atherosclerosis. Journal of Chinese Integrative Medicine, 2012, 10(7): 814-820.
[3] Mao Mei-jiao, Hu Jun-ping, Chen Fu-rong, Zhang Yi-yi, Liu Ping. Effects of Chinese herbal medicine Guanxinkang on lipid metabolism and serum C-reactive protein, amyloid A protein, and fibrinogen in apolipoprotein E-knockout mice with atherosclerosis. Journal of Chinese Integrative Medicine, 2011, 9(3): 306-312.
[4] Mei-jun Lü, Hui-yong Zhang, Zhe Zhang, Guan-lin Yang. Measurement of health-related quality of life in coronary heart disease: A review. Journal of Chinese Integrative Medicine, 2011, 9(12): 1277-1285.
[5] Jian-peng Du, Da-zhuo Shi , Tian-chang Li, Hao Xu, Hao Chen. Correlation between blood stasis syndrome and pathological characteristics of coronary artery in patients with coronary heart disease. Journal of Chinese Integrative Medicine, 2010, 8(9): 848-852.
[6] Dong-taoLi , Jie Li, Jian Wang, Fu-yu Li, Jing-xiu Zhu, Mei-zeng Zhang, Jun-yan Li, Yan-lai Xu, Ling-bo Wei , Wen-yan Ji, Rong-qin Jiang, Xue-fa Liu. Quantitative evaluation of the degrees of qualitative syndromes commonly encountered in patients with coronary heart disease. Journal of Chinese Integrative Medicine, 2010, 8(8): 750-756.
[7] Mei Xue , Ke-ji Chen, Hui-jun Yin. Relationship between polymorphism of platelet membrane glycoprotein Ⅲa and coronary heart disease with blood-stasis syndrome in Chinese Han population. Journal of Chinese Integrative Medicine, 2009, 7(4): 325-329.
[8] Jie Wang, Qing-yong He, Zhan Shi, Yan-wei Xing, Ji Li, Yu-tao Fang, Yan-li Tang. Correlation between syndrome factor combination and cardiac function as well as blood-lipid in coronary heart disease. Journal of Chinese Integrative Medicine, 2008, 6(9): 897-901.
[9] Jie Wang, Yan-wei Xing, Jian-xin Chen, Qing-yong He, Yong-hong Gao, Zun Li. Characteristics of coronary arteriography and traditional Chinese medicine syndrome of 1 069 patients with coronary artery disease. Journal of Chinese Integrative Medicine, 2008, 6(2): 148-152.
[10] Mei Xue, Ke-Ji Chen, Xiao-juan Ma, Jian-gang Liu, Yue-rong Jiang, Yu Miao, Hui-jun Yin. Effects of Xuefu Zhuyu Oral Liquid on hemorheology in patients with blood-stasis syndrome due to coronary disease and their relationship with human platelet antigen-3 polymorphism. Journal of Chinese Integrative Medicine, 2008, 6(11): 1129-1135.
[11] Shuo Zhang, Yan-qin Song, Wang Yue, Xing-rong Mao, Chuan-xia Ju, Meng-jiu Dong, Qiong-li Zheng, Xiao-hua Dai, Zhong-ye Li. Multicentric randomized double blinded clinical study of Yiqi Tongmai Oral Liquid against angina pectoris in patients with coronary heart disease. Journal of Chinese Integrative Medicine, 2007, 5(4): 383-391.
[12] Lin Li​, Xiao-dong Li​, Jian-nan Song​, Xiang-zhong Fang​, Yang Miao​, Qian Lin​. Applying matching matrix, factor analysis and clustering analysis to investigation of characteristics of syndromes of phlegm and blood stasis in patients with coronary heart disease. Journal of Chinese Integrative Medicine, 2006, 4(4): 343-347.
[13] Yan-sheng Huang, Shu-ren Wang, Yan-fang Zhi, Shen-yan Kong, Lin Sun​, Yu Wu​, Jian-min Lu​, Fu-min Dai​. Effects of Xuezhikang Capsules on vascular endothelial function and redox status in patients with coronary heart disease. Journal of Chinese Integrative Medicine, 2006, 4(3): 251-255.
[14] Qin Feng, Yi-yang Hu. Syndromes and pathological mechanism of insulin resistance in traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2005, 3(1): 63-65.
[15] Ning Du, Yong Xu. Medical value of isoflavones. Journal of Chinese Integrative Medicine, 2003, 1(4): 296-300.
Full text



[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278