摘要
目的:首次应用国内最先进的基因测序技术为基础,研究冠心病(CHD)的载脂蛋白E(ApoE)基因多态性分布,探究ApoE基因多态性与CHD中医证型的相关性,为CHD中医辨证施治理论提供分子生物学依据。方法:将118例CHD患者设立为试验组,另设立123例正常人群为对照组,通过基因测序法得出:CHD组和对照组ApoE基因表型分布和等位基因频率,并进行统计学分析。结果:118例CHD患者,根据辨证分型标准,共分为以下6型:阴寒凝滞证13例(占总例数的11.02%,以下同),痰浊壅塞证29例(24.58%),心血瘀阻证33例(27.96%),心肾阴虚证11例(9.32%),气阴两虚证27例(22.88%),阳气虚衰证5例(4.24%)。CHD组E2/4、E3/4、E4/43种基因型频率较对照组有增加的趋势,差异有统计学意义﹙χ2=5.004,P<0.05);而E3/3基因型其频率较对照组则有减少的趋势,差异有高度统计学意义﹙χ2=6.8743,P<0.01)。CHD组ε3等位基因分布频率明显低于对照组(χ2=9.2898,P<0.05),而ε4等位基因分布频率则明显高于对照组(χ2=13.927,P<0.01),差异有高度统计学意义。CHD组不同中医证型ApoE等位基因频率比较,则发现:心血瘀阻证、气阴两虚证二种证型ε4等位基因频率明显高于阴寒凝滞证、痰浊壅塞证、心肾阴虚证、阳气虚衰证四种证型(P<0.05);ε3等位基因频率不同中医证型间则大致相等;ε2等位基因频率不同中医证型间心血瘀阻证较低,而阴寒凝滞证、心肾阴虚证、阳气虚衰证较高。ApoE基因E4/2+E3/4+E4/4型中:痰浊壅塞证、心血瘀阻证、气阴两虚证相互比较P>0.05,痰浊壅塞证、心血瘀阻证、气阴两虚证3种证型与阴寒凝滞证、心肾阴虚组证、阳气虚衰证3种证型比较P<0.05。结论:CHD的主要基本证型为心血瘀阻证、痰浊壅塞证、气阴两虚证,并与ApoEE3/4、E4/4基因表型及ε4等位基因密切相关;ε4基因是CHD的易感等位基因,是CHD发生的重要遗传易患因素,ε3等位基因可视为CHD发生的保护因素;ApoE基因多态性、血脂水平与CHD不同中医证型之间存在因果关系,ApoE基因可通过血脂代谢作用而影响CHD的发病。
Objective :Study distribution of ApoE polymorphism in CHD by first applying the most advanced gene se- quence testing technique, and to find the possibility of Traditional Chinese Medicine and Polymorphism of ApoE Gene in CHD,provding molecular biology envidences for CHDtreating of TCM. Methods: Make 118 CHD patients as the experient group,while another 123 healthy ones belong to the control group . Through the DNA sequencing analysis to determine ApoE phenotype distribution and allele frequency of the two groups and get the statistic analysis. Results : 3 kinds of ho- mozygote and 3 kinds of heterozygote of 118 CHD patients, namely E2/2, E3/3, E4/4 were detected, among most of which are ApoE gene phenotype. The genotypic frequency of FA/2, E3/4, E4/4 in experiment groups increased than those of control group ( X 2 = 5. 004, P 〈 0.05). The genotypic frequency of E3/3 in experiment groups decreased than those of control group ( X2 = 6. 8743 ,P 〈0.01 ). Compared with 123 samples of control group,the genotypic frequency of ε3 allele decreased significantly(X2 = 9.2898, P 〈 0.05 ) and which of ~,4 allele increased signifieantly( X2 = 13.927 ,P 〈 0.01 ). The highly proportion of E4/2 + E3/4 + E4/4 genotypie frequency in 118 CHD patients belongs to ariae blood stasis,tanzuo impotency and deficiency of both vital energy and yin( 82.93% ),followed by E3/3 genotypie frequency ( 75.00% ) and E2/2 + E2/3 genotypic frequeney( 61.90% ) of which is the lowest. The proportion of genotypie frequen- cy in pattern of syndrome of Traditional Chinese Medicine (TCM) of ariac blood stasis,tanzuo impotency and deficieney of both vital energy and yin is significant different to that cold accumulation of heart meridian, deficiency of heart and kid- ney - YIN and deficient and weak YANG QI ( P 〈 0.05 ), among which the genotypic frequency of ~,4 allele increased significantly ands2 witha3 is equally. Compared ApoE gen E4/2,E3/4, E4/4 pattern of syndrome of TCM of ariac blood stasis, tanzuo impotency and deficiency of both vital energy ( P 〉 0.05 ), while compare that with the other three ( P 〈 0.05 ). Conclusion: The main patterns of syndrome of TCM are ariac blood stasis, tanzuo impotency and deficiency of both vital energy and yin. The genee4 allele is the suscepfive allele in CHD and the important factor of genetic liability. The genee3 allele can be a protective factor on CHD occurrence. Causality does exist among ApoE gene polymorphism, se- rum lipid level and different TCM patterns of CHD. Polymorphism of ApoE gene in CHD earl interfere the occurrence of CHD by way of influencing metabolism of blood fat.
出处
《中华中医药学刊》
CAS
2009年第11期2323-2330,共8页
Chinese Archives of Traditional Chinese Medicine
基金
江苏省自然科学基金课题(BK2006157)
关键词
APOE基因多态性
冠心病
中医证型
辨证施治
polymorphism of apoE gene
CHD
pattern of syndrome of TCM
confirming treatment according to different syndromes