趋化因子及其受体基因多态性与心肌梗死发生的相关性研究  

Association of chemokines and their receptors genes polymorphisms with risk of myocardial infarction

作　　者：许鑫[1] 王力涵[1] 刘海波 徐长福[3] 张鹏[4] 雍粉娣[5] 施育平[1] 

机构地区：[1]浙江大学医学院附属第二医院心内科,杭州310009 [2]浙江省宁波市鄞州人民医院心内科 [3]浙江省中医药大学附属第二医院心内科 [4]浙江省绍兴市人民医院心内科 [5]浙江省嘉兴市第一医院心内科

出　　处：《中华医学遗传学杂志》2013年第5期601-607,共7页Chinese Journal of Medical Genetics

基　　金：浙江省自然科学基金（Y206531）;浙江省科技攻关计划、重点科研项目（021103166）

摘　　要：目的初步探讨趋化因子（chemokines，CCL5，CCL2）和相应受体（chemokine receptor，CCR5，CCR2）的基因多态性与中国汉族人群心肌梗死（myocardial infarction，MI）的相关性。方法采用病例对照研究，选取心肌梗死或陈旧性心肌梗死患者634例（MI组）和正常对照601名。采用聚合酶链反应一限制性片段长度多态性方法检测受试者CCL5rs2107538（-403G／A）、CCL2rsl024611（-2518A／G）、CCR5rs333（A32ins／del）和CCR2rsl799864（190G／A）的基因型，并用DNA测序法鉴定部分结果。结果所有受试者中均未发现CCR5△32突变基因型。CCL2rs1024611和CCR2rs1799864基因型和等位基因频率在MI组与对照组的分布差异无统计学意义。CCL5rs2107538基因多态性与MI发生相关，MI组AA基因型频率明显高于对照组（12．1％VS．5．0％，P〈0．01），经校正后可显著增加MI的风险（校正后OR=3．346，95％CI—1．938～5．775，P〈0．01），A等位基因频率明显高于对照组（26．6％VS．21．8％，P=0．006）。CCL5rs2107538（-403G／A）和CCL2rsl024611（-2518A／G）处于强连锁不平衡状态，M1组A-403-A—2518单体型频率和AA／AA结合基因型频率明显高于对照组，可独立增加MI的风险（A-403-A-2518单体型：校正后OR=1．229，95％CI—1．012-1．493，P=0．038；AA／AA结合基因型：校正后OR=3．245，95％CI=1．780～5．914，P〈0．01）。结论CCL5rs2107538基因多态性与MI的发生相关，其中AA基因型可能是MI发病的独立危险因子，A等位基因可能是MI的易感基因。Objective To assess the association of variations in chemokines （CCL5, CCL2）, chemokine receptor （CCR5 and CCR2） genes with susceptibility to myocardial infarction（MI） through a casecontrol study. Methods Genotypes of patients with MI（n=634） were compared with those of controls（n= 601）. Genetic polymorphisms of CCL5 rs2107538 （ -403G/A）, CCL2 rs1024611 （ -- 2518A/G）, CCR5 rs333（A32 ins/del） and CCR2 rs1799864（190G/A） of 1235 individuals were determined with polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP）. Particular genotypes were confirmed with DNA sequencing. Results No subject was found to carry the CCR5 -- A32 allele. No association was found between CCL2 rs1024611 and CCR2 rs1799864 polymorphisms and MI. For CCL5 rs2107538 polymorphism, A allele has occurred at a higher frequency in MI patients than controls, and its AA genotype has been associated with a significantly increased risk of MI independent of conventional risk factors（OR= 3. 346, 95%CI= 1. 938-5. 775, P〈0.01, AA vs. GG）. Further analysis indicated that MI patients had significantly more A 4o3--A 251% haplotype （CCL5 --403G/A/CCL2 --2518A/G, 21.8% vs. 26.6%, OR=I. 229, 95%CI=1. 012-1. 493, P=0. 038） and AA/AA genotype （CCL5 -403G/A/CCL2 -2518A/G, 5.0% vs. 12.1%, OR=3.245, 95%CI=1. 780-5. 914, P〈0.01）. Conclusion Although our data does not support an association between CCL2 rs1024611, CCR2 rs1799864 and CCR5 rs333 polymorphisms and MI, genetic variation in CCL5 gene may still be a useful marker for assessing susceptibility to MI in ethnic Han Chinese population.

关 键 词：趋化因子基因 趋化因子受体基因 遗传多态性 心肌梗死 

分 类 号：R542.22[医药卫生—心血管疾病]