炎症细胞因子CRP/IL-6/IL-10多态性与社区获得性肺炎易感性及严重程度的关联研究

Correlation of IL-6/CRP/IL-10 polymorphisms with the susceptibility and severity of community-acquired pneumonia

目的探讨炎症细胞因子IL-6/CRP/IL-10多态性与社区获得性肺炎(community-acquired pneumonia,CAP)易感性及严重程度的关联。方法选择2012年10月-2014年6月就诊于我院的366例CAP患者作为CAP组,另选同期405名健康体检者作为对照组。应用限制性片段长度多态性聚合酶链反应(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)对所有受试者的CRP 1059G/C、IL-6-597G/A和IL-10-592C/A进行基因型分析,收集所有受试者临床资料,并采用CURB-65和PSI评分衡量CAP患者易感性、严重程度及预后。结果 CAP组IL-6-597G/A的AA+AG基因型和A等位基因频率均高于对照组(均P<0.05),A等位基因可能是发生CAP的危险因子。CAP组IL-10-592C/AAA基因型和A等位基因频率均高于对照组(均P<0.05)。SCAP组(重症肺炎组)的死亡率、呼吸衰竭比率、脓毒性休克比率、多器官功能障碍综合症(Multiple organ dysfunction syndrome,MODS)比率、APACHEⅡ评分和住院天数均明显高于NSCAP(非重症肺炎组)组(均P<0.05)。SCAP组中IL-6-597G/A A等位基因携带者分布频率高于NSCAP组(P<0.05)。IL-10-592C/A在SCAP组中AA基因型及A等位基因的频率均明显高于NSCAP组(均P<0.05)。携带IL-6-597G/A突变基因型(GA+AA)的肺炎患者白细胞数、中性粒细胞数、血沉均明显高于野生基因型携带者GG(均P<0.05)。携带IL-6-597G/A突变基因型(GA+AA)的患者在死亡组中的比例远高于存活组(P<0.05)。携带IL-6-597G/A突变基因型(GA+AA)的肺炎患者CURB-65和PSI评分均明显高于野生基因型携带者GG(均P<0.05)。此外,携带IL-10-592C/A突变基因型(CA+AA)的肺炎患者CURB-65和PSI评分也均明显高于野生基因型CC携带者,且差异均有统计学差异(均P<0.05)。结论 IL-6-597G/A和IL-10-592C/A与CAP的发生发展以及严重程度相关,而CRP 1059G/C则与CAP的发生发展以及严重程度无关。

Objective To explore the correlation of IL-6/CRP/IL-10 polymorphisms with the susceptibility and severity of community-acquired pneumonia. Methods A total of 366 CAP patients were enrolled as the case group and 405 healthy individuals as control group. PCR-RFLP was performed to analyze CRP 1059G/C, IL-6-597G/ A and IL-10-592C/A genotypes. CURB-65 score and PSI score were used to measure susceptibility, severity and prognosis of CAP. Results When compared with the control group, wild genotype （AA/AG） frequency of IL-6 597G/A and A allele frequency, IL-lO-592C/A AA genotype and A allele were higher in the CAP group （ all P 〈 0. 05）. Comparing with the non-severe community-acquired pneumonia （NSCAP） group, the distribution frequency of IL-6 -597G/A A allele carrier was higher in the SCAP group （ P 〈 0.05 ）. In terms of white blood ceils count, neutrophil cells count and erythrocyte sedimentation rate （ESR）, CAP patients who carried IL-6-597G/A mutant genotype were higher than wild genotype GG carriers, and all differences were statistically significant （ all P 〈 0. 05 ）. Besides, comparing with the survival group, the proportion of patients carrying IL-6 -597G/A mutant genotype （GA ＋ AA） was far higher in the death group （ P 〈 0.05 ）. When compared with wild genotype carriers （ GG）, CURB-65 score and PSI score were significantly higher in CAP patients carrying IL-6 -597G/A mutant genotype （GA ＋ AA） （ both P 〈 0. 05）. Furthermore, CURB-65 score and PSI score were significantly higher in CAP patients carrying IL- 10 -592C/A mutant gcnotype （CA ＋ AA） than that in wild genotype carrier （CC） （both P 〈 0. 05）. Conclusion IL-6 -597G/A and IL-10 -592C/A are associated with the occurrence and development of CAP and its severity of CAP, while there is no association of CRP 1059G/C with CAP and its severity.