慢性阻塞性肺疾病急性加重期患者血清白介素-13表达及其基因多态性的意义

Expression of Serum Interleukin-13 and Its Polymorphism on the Patients with Chronic Obstructive Pulmonary Disease in Acute Exacerbation Period

目的探讨慢性阻塞性肺疾病(慢阻肺)急性加重期患者血清白介素-13(IL-13)的变化,及其基因多态性与血清IL-13的相关性。方法纳入2014年12月至2016年3月于福建省立医院呼吸科病房住院的慢阻肺急性加重期患者共54例(慢阻肺急性加重组),及同期正常体检人员33例(对照组),皆抽取空腹外周血5m L,采用酶联免疫吸附测定法(ELISA)测定其血清IL-13,采用聚合酶链反应(PCR)结合基因测序方法检测IL-13+1923C/T、+2044G/A基因多态性。54例中病情好转期患者30例(慢阻肺好转组),于入院后1周抽取空腹外周血3m L采用ELISA法测定其血清IL-13。统计分析比较慢阻肺急性加重组与对照组的血清IL-13及基因多态性,及慢阻肺急性加重期与好转期的血清IL-13变化。结果慢阻肺急性加重组血清IL-13水平低于对照组[(47.8±42.7)比(70.6±53.6)μg·L-1,P<0.05],IL-13+1923C/T与+2044位点G/A显著相关(R2=0.911,P=0.000<0.001);+1923位点等位基因C、T频率在两组间分布的差异不具有显著性(χ2=0.915,P>0.05),慢阻肺急性加重组等位基因C、T的频率为71.3%、28.7%;血清IL-13在T携带基因组与CC基因组之间的差异及在A携带基因组与GG基因组之间的差异均无统计学意义(均P>0.05)。结论慢阻肺急性加重组血清IL-13特异性下降,IL-13+1923C/T与+2044位点G/A连锁不平衡,IL-13+1923位点T等位基因、+2044位点A等位基因与慢阻肺易感性不相关。

OBJECTIVE To explore the expression of serum interleukin-13 （IL-13） on the patients with chron- ic obstructive pulmonary disease （COPD） in acute exacerbation period, the correlation between the single nucleotide polymorphisms （SNPs） of IL-13 gene and the IL-13 levels. METHODS Total 54 patients with COPD in acute ex- acerbation period admitted in the respiratory ward of Fujian Provincial Hospital from December,2014 to March,2016 were included as COPD group in acute exaxerbation period. Total 33 healthy controls were included as control group. Each individual had the extraction of fasting peripheral blood 5mL. The IL-13 levels were determined by en- zyme-linked immunosorbent assay （ELISA）. IL-13 gene polymorphisms in ＋ 1923C/T site and ＋ 2044 site were gen- otyped in these two groups by using polymerase chain reaction （PCR） combined with gene sequencing meth- ods. About 7 clays after admission, thirty patients among the 54 patients with improved period of COPD were included as COPD improvement group, all had the extraction of peripheral blood 3mL for IL-13 detection determined by ELISA. The expression of serum IL-13 and gene polymorphisms between COPD group in acute exacerbation period and control group were analyzed statistically. The changes of serum IL-13 between two COPD groups were also ana- lyzed statistically. RESULTS The IL-13 levels of the COPD group in acute exarcerbation period were lower than that of control group [ （47.8 ±42. 7） to （70. 6 ±53.6） μg· L-1 ,P 〈0. 05] ,the SNP ＋ 1923C/T site was in strong linkage disequilibrium with the SNP IL-13 ＋ 2044G/A site （R2 =0. 911 ,P =0. 000）. There was no significant differ- ence of the distribution of genotype in ＋ 1923C/T site of IL-13 gene between the two groups （X2 = 0. 915, P 〉 0. 05）. In the COPD group in acute exarcerbation period,the C and T allele frequencies at 1923 locus of IL-13 genewere 71.3% and 28. 7%. There were no significant difference of the serum IL-13 and the total serum IgE levels be- tween allele T_ groups and allele CC group, also no significant difference between A_ groups and allele GG group（P 〉0. 05）. CONCLUSION The IL-13 levels were decreased specifically in the COPD group in acute exarcerbation period. The SNP ＋ 1923C/T site and the SNP ＋2044G/A site were in strong linkage disequilibrium. The SNPs of IL- l3 ＋ 1923 and ＋ 2044 were not significantly associated with the susceptibility to COPD.