蛋白C基因变异与汉族人群急性呼吸窘迫综合征的易感性相关  

Protein C genetic variation was associated with the susceptibility to acute respiratory distresssyndrome in Chinese Han population

作　　者：张瑾[1] 童朝阳[1] 尹俊[1] 孙思[1] 宋振举[1] 

机构地区：[1]复旦大学附属中山医院急诊科,上海200032

出　　处：《中华急诊医学杂志》2017年第6期632-637,共6页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金（81471840,81171837）;上海市中医药发展三年行动计划（ZY3-CCCX-3-3018,ZHYY-ZXYJH-201615）;复旦大学附属中山医院优秀骨干人才培养基金;国家临床重点专科建设项目

摘　　要：目的探讨蛋白C （protein C, PC）和内皮细胞活化蛋白C受体（endothelial protein C receptor, EPCR）基因变异与汉族人群急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS）遗传易感和预后相关性。方法收集275例ARDS患者和337例对照患者（入住ICU，具有ARDS发病的高危因素，而未进展至ARDS）入选本研究。共选择PC和EPCR基因的5个tagSNPs进行研究，以SNPstream技术平台进行分型。ELISA方法测定血浆活化蛋白C （activated protein C, APC）的浓度。结果PC基因rs1799809和rs1158867高度连锁，且与ARDS的发病相关。rs1799809和rs1158867（T/C）等位基因频率在ARDS组和对照组之间差异具有统计学意义（P=0.00 11，P=0.00 16），ARDS组等位基因rs1799809T的频率为87.9%，明显高于对照组（81.1%）（OR=1.569, 95%CI 1.192～2.066）。rs1799809基因型TT、TC和CC的频率在两组之间差异具有统计学意义（P=0.007）。Haplotype分析发现由PC基因3个SNPs （rs1799809、rs1158867和rs2069912）组成的单倍域与ARDS的发病明显相关，单倍型CCC的频率在两组之间差异具有统计学意义（P=0.002），ARDS患者单倍型CCC的频率（10.8%）明显低于对照组（16.9%）。另外研究发现携带rs1799809基因型TT的ARDS患者，外周血APC的浓度低于携带基因型TC和CC的患者（Padj= 0.02）。EPCR基因的2个SNPs等位基因和基因型频率两组相比差异无统计学意义。结论PC基因变异与中国汉族人群ARDS的遗传易感性相关，其基因结构变异影响ARDS患者血浆APC的浓度。ObjectiveTo investigate the genetic variants in the protein C （PC） and endothelial protein C receptor （EPCR） genes associated with the risk and outcome of acute respiratory distress syndrome （ARDS） patients in Chinese Han race.MethodsFive tagSNPs （single nucleotide polymorphism, SNP） in the PC and EPCR genes were genotyped in patients with ARDS （n =275） and non-ARDS （n=337） in order to find the association between them in this case-control study. The SNPs were genotyped by SNPstream Beckman platform. Then, the correlation between the associated SNPs and plasma levels of activated protein C （APC） in patients with ARDS was investigated. The APC levels were measured using enzyme linked immunosorbent assay （ELISA） method.ResultsAssociation analysis revealed that two PC SNPs in perfect linkage disequilibrium, rs1799809 and rs1158867, were significantly associated with susceptibility to ARDS. T allele frequency of rs1799809 in ARDS patients was significantly higher than that in non-ARDS patients （OR=1.569, 95%CI： 1.192-2.066）. And the genotype frequencies of rs1799809 were also significantly different between these two groups （P=0.007）. The association remained significant after adjustment for multiple comparisons. Haplotype consisting of three SNPs in the PC gene was also associated with susceptibility to ARDS. The frequency of haplotype CCC in the ARDS samples was significantly lower than that in the non-ARDS group （P〈0.01）. Moreover, ARDS patients carrying rs1799809 TT genotype showed lower serum levels of APC than patients with TC and CC genotypes （Padj=0.02）. However, genotype and allele analyses of EPCR did not show any significant difference between ARDS and non-ARDS patients.ConclusionsThese findings indicated that common genetic variation in the PC gene was significantly associated with susceptibility to ARDS in Chinese Han race. The PC genetic variation influenced plasma concentration of APC in patients with ARDS.

关 键 词：蛋白C 活化蛋白C 内皮细胞活化蛋白C受体 基因变异 SNPs 急性呼吸窘迫综 合征 易感性 预后 

分 类 号：R563.8[医药卫生—呼吸系统]