环氧化酶和血红素氧合酶1基因多态性与阿司匹林抵抗关系的研究  

Relation of cyclooxygenase and heme oxygenase-1 genetic polymorphisms with aspirin resistance

作　　者：范利[1] 李晓利[2] 赵莉[3] 马飞 陈荣霞 曹剑[1] 刘霖[1] 王强[2] 陈昕[2] 孙沛[2] 

机构地区：[1]解放军总医院南楼心血管一科,北京100853 [2]解放军309医院 [3]保定市第一医院 [4]总装备部北京第二干休所

出　　处：《中华老年心脑血管病杂志》2012年第8期805-809,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家科技支撑计划(2009BAI86B04);全军医药卫生科研基金(07BJZ01)

摘　　要：目的探讨环氧化酶1(COX-1)、COX 2和血红素氧合酶1(HO-1)的基因多态性与阿司匹林抵抗(AR)的相关性。方法选择431例老年汉族心脑血管病患者,持续服用(75～100 mg)阿司匹林≥1个月,通过花生四烯酸诱导光比浊法联合二磷酸腺苷诱导光比浊法,筛查出AR患者(AR组)36例,阿司匹林半抵抗患者(semi-AR组)164例和阿司匹林不抵抗患者(non-AR组)231例。并对COX-1 rs1888943、rs1330344、rs3842787、rs5787、rs5789和rs5794,COX-2 rs20417和rs5277,HO-1 rs2071746共9个单核苷酸多态性位点的相关性进行比较。结果与non-AR组和semi-AR组比较,AR组COX-1 rs1330344(1 676A/G)突变的G等位基因增加了发病风险(OR=1.77,95%CI:1.07～2.92,P=0.02)和(OR=1.66,95%CI:0.99～2.77,P=0.05)。HO-1 rs2071746(-413 A>T)突变T等位基因同样增加了发病风险(OR=1.70,95%CI:1.02～2.79,P=0.04)和(OR=1.68,95%CI:1.00～2.80,P=0.05)。结论 COX-1 rs1330344和HO-1 rs2071746与老年汉族人群AR相关,COX-1 rs1888943、rs3842787、rs5787、rs5789、rs5794和COX-2 rs20417、rs5277与AR不相关,在汉族人群中罕见出现。Objective To study the relation of cyclooxygenase-1 （COX-l）, cyclooxygenase-2 （COX-2） and heine oxygenase 1 （HO-1） genetic polymorphisms with aspii＇in resistance（AR）. Methods Four hundred and thirty-one elderly Han patients with cardio-cerebrovascular diseases, who consecutively took aspirin 1 month（75--100 mg daily）,were divided into aspirin resistance （AR） group（n=36）,semi-AR group（n=164）,and non-AR group（n=231） according to the com- bined arachidonic acid and adenosine diphosphate-induced light turbimetry findings. Relation of COX-1 （rs1888943,rs1330344, rs3842787, rs5787, rs5789, rs5794）, COX-2 （rs20417, rs5277） and HO-l（rs2071746） genetic polymorphisms was compared. Results The risk of developing cardio- cerebrovascular diseases due to mutated G alleles in COX-1 （rs1330344,-1676A/G）and T alles in HO-1（rs2071746 ,-413 A^T）was significantly higher in AR group than in non-AR and semi-AR groups（OR= 1.77,95% CI：1.07--2.92,P=0.02 and OR=I. 66,95 % CI：0.99--2.77,P=0.05% OR=I. 70,95% CI： 1.02--2.79,P=0.04 and OR=I. 68,95% CI：l. 00--2.80,P=0.05）. Conclusion COX-l（rs1330344） and HO-1（rs2071746） are related with AR in elderly Han populations. However, COX-1 （rs1888943, rs3842787, rs5787, rs5789, rs5794） and COX-2 （rs20417 and rs5277） ,rarely detected in elderly Han populations,are not related with AR.

关 键 词：环氧化酶1 血红素加氧酶1 多态性 单核苷酸 阿司匹林 花生四烯酸 等位基因 

分 类 号：R54[医药卫生—心血管疾病] R743[医药卫生—内科学]