白细胞介素8单核苷酸多态性与呼吸道合胞病毒易感性关联的研究

Association of interleukin 8 single nucleotide polymorphisms with the susceptibility to respiratory syncytial virus infection

目的探讨白细胞介素8(IL-8)-251T/A 和781 C/T单核苷酸多态性(SNP)与呼吸道合胞病毒(RSV)易感性的关系。方法采用等位基因特异性聚合酶链反应(AS-PCR)技术,对101例 RSV 肺炎、108例非 RSV 肺炎住院患儿及35个核心家系的两个 SNP 位点的基因型进行检测,通过基因测序进行验证。用病例-对照和传递不平衡检验(TDT)分析 SNP 位点等位基因的分布,并对两个SNP 位点的连锁和单体型进行分析。结果 (1)病例组 IL-8-251T 的频率显著增加(OR=2.08,P=0.0002,病例-对照分析;LRT=14.31,P=0.0008,TDT)。(2)IL-8-251T 与781C 是连锁的(D′=0.607±0.03,r^2=0.2861,P=0.0000)。(3)病例组 TC 单体型的频率显著增加(P=0.01)。结论IL-8-251T 与781 C 形成的 TC 单体型与 RSV 易感性存在关联,即部分 RSV 易感基因可能存在于含有 TC 单体型的基因片段中或者与该段基因紧密连锁。

Objective To explore the association of interleukin 8（IL-8） -251T/A and 781 C/T single nucleotide polymorphisms （SNPs） with the susceptibility of infants and young children to respiratory syncytial virus（ RSV）infection. Method This study included 101 hospitalized patients under 2 years of age who suffered from RSV pneumonia, 108 hospitalized patients under 2 years of age with non-RSV pneumonia and 35 core families with a child hospitalized for RSV pneumonia. Genotypes of 2 SNP loci in all enrolled persons were defined by allele specific polymerase chain reaction （AS-PCR）, and confirmed by gene sequencing. The allele＇s frequencies of SNPs were analyzed with case-control study and transmission disequilibrium test （TDT）, linkage of 2 loci and haplotypes composed of the 2 loci were also studied. Results （ 1 ） The frequency of IL-8 - 251T in cases was dramatically high （ OR = 2. 08, P = 0. 0002, casecontrol study;LRT= 14. 31, P =0.0008, TDT）. （2）IL-8 -251T and 781C was linkaged（D＇ =0.607 ± 0.03,r^2 =0.2861,P =0.0000）. （3） Haplotype of TC was significantly high in cases （P =0.01）. Conclusion These findings support that haplotype of TC composed of IL-8 -251T and 781C is associated with the susceptibility to RSV, namely, some RSV predisposing genes are located in the gene fragment including TC haplotype or linked tightly with this gene fragment.