摘要
目的:探讨COX1-1676C/T及IL-1β-511C/T基因多态性与肠溶阿司匹林(ASP)致冠心病(CHD)患者上消化道出血的关系。方法:收集4组资料各100例:连续服用肠溶阿司匹林超过10d且大便潜血试验阳性[ASP+(OB+)]的CHD患者100例,按年龄、性别配对原则,收集大便潜血试验阴性[ASP+(OB-)]的CHD、未服用ASP但上消化道出血者[ASP-(OB+)]和健康对照者[ASP-(OB-)]各100例。应用PCR-RFLP方法进行COX1-1676C/T和IL-1β-511C/T基因分型,并测定服药前后ASP+(OB+)组(42例)和ASP+(OB-)组(42例)IL-1β及血管内皮生长因子(VEGF)的含量。结果:对于COX1-1676C/T基因,ASP+OB(+)组中的T等位基因频率高于其他3组(P<0.05),并且该组服药前后携带TT型者比其他基因型者VEGF明显下降(P<0.05),携带T等位基因者IL-1β明显升高(P<0.05)。对于IL-1β-511C/T,OB(+)组的TT型和T等位基因频率均高于(OB-)组(P<0.05),并且ASP+OB(+)组携带TT型者比携带其他基因型者VEGF下降明显而IL-1β升高明显(P<0.05)。结论:COX1-1676C/T T等位基因可能是肠溶ASP致CHD患者上消化道出血的易感因素,IL-1β-511C/T突变可能是上消化道出血的易感因素;其机制可能是2个基因突变后诱导血清中IL-1β水平增加和VEGF水平降低。
OBJECTIVE To investigate the relationship between genetic polymorphisms of COX1-1676C/T and IL-1β-511C/T and upper gastrointestinal hemorrhage induced by enteric-coated aspirin in coronary heart disease（CHD） patients.METHODS 400 cases were enrolled in this study：100 CHD cases of taking aspirin for more than 10 days and the positive fecal occult blood test,100 CHD cases of taking aspirin for more than 10 days but the negative fecal occult blood test,100 cases of positive fecal occult blood test in the upper gastrointestinal hemorrhage,100 healthy volunteer.PCR-RFLP genotyping procedures of alleles COX1-1676C/T and IL-1β-511C/T were performed.Serum IL-1β and VEGF concentrations were determined before and after ASP treatment in 42 CHD patients of ASP＋（OB＋） and in 42 CHD patients of ASP＋（OB-）.RESULTS The T allele frequencies of COX-1-1676C/T in ASP＋OB（＋） group were higher than those in the three groups（P0.05）,the degree of the decrease of VEGF level in TT genotype was significantly higher than other genotypes（P0.05）,the degree of the increase of IL-1β level in TT genotype and T allele were significantly higher than other genotypes（P0.05）.In the two OB（＋） groups,TT genotype frequency and T allele frequency of IL-1β-511C/T were significantly higher than those in the two OB（-） groups（P0.05）.Regard ASP＋OB（＋）,the degree of the decrease of VEGF level and the increase of IL-1β in TT genotype of IL-1β-511C/T gene was significantly higher than other genotypes（P0.05）.CONCLUSION COX1-1676 T allele may be an important factor of upper gastrointestinal hemorrhage induced by enteric-coated aspirin.IL-1β-511 C/T mutation may be a dangerous factor of upper gastrointestinal hemorrhage.The two mutations can decrease VEGF levels and increase IL-1β levels,which may lead to upper gastrointestinal hemorrhage induced enteric-coated aspirin in CHD patients.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2012年第21期1691-1695,共5页
Chinese Journal of Hospital Pharmacy
基金
福建省卫生教育联合攻关计划项目(No:WKJ2008-2-59)
中华医学会临床医学科研专项资金(No:09010150170)
关键词
COX1
IL-1Β
基因多态性
肠溶阿司匹林
上消化道出血
cycloxygenase-1
interleukin-1β
gene polymorphism
enteric-coated aspirin
upper gastrointestinal hemorrhage
