肿瘤坏死因子和白细胞介素-1基因多态性与急性呼吸窘迫综合征的相关性研究

Study on the association between cytokine gene polymorphisms and acute respiratory distress syndrome

目的 :探讨肿瘤坏死因子 (TNF)α、TNFβ、白细胞介素 (IL) 1β和白细胞介素受体拮抗剂 (IL 1ra)基因多态性与急性呼吸窘迫综合征 (ARDS)易感性及预后的相关性。方法 :以 2 0 0 1～ 2 0 0 2年本院ICU收治的 2 7例ARDS患者为研究对象 ,以正常献血者为对照。提取全血基因组DNA ,应用聚合酶链反应 (PCR )和限制性长度片段多态性 (RFLP)方法检测细胞因子TNFα、TNFβ和IL 1β基因多态性 ,PCR法检测IL 1ra基因内含子 2区多态性区域含有 86bp的同向重复结构可变数 (VN TR)。结果 :与对照组比较 ,ARDS患者TNFα、TNFβ和IL 1β基因型和等位基因频率分布无显著性差异。对照组IL 1ra等位基因A2 的检出率为 7.5 % ,ARDS患者的检出率为 16.7% ,有增高趋势 ,但无显著性差异 (P =0 .0 84)。ARDS存活患者TNFβ等位基因 1的检出率为 47.1% ,显著低于ARDS病死组 ( 80 .0 % ) ,等位基因 1携带者病死的相对危险度为 4.5。但TNFα、TNFβ和IL 1β和IL 1ra的基因型频率在ARDS存活和病死患者之间无显著性差异 (P >0 .0 5 )。 结论 :TNFα、IL 1β和IL 1ra基因多态性可能不是决定ARDS发病及预后的主要遗传信息 ,但TNFβ等位基因 1和

Objective To investigate the correlations between the polymorphisms of TNFα,TNFβ,IL-1β and IL-1ra gene and the susceptibility or outcome of ARDS.Methods A prospective,consecutive entry study was made among 27 patients with ARDS admitted in ICU between 2001 and 2002.The genomic DNA of peripheral blood nucleated was extracted.The region containing the polymorphism sites of TNFα,TNFβ and IL-1β gene was amplified by polymerase chain reaction (PCR) and restrictive fragment length polymorphism (RFLP).The polymorphic region within intron 2 of the IL-1ra gene was amplified by PCR.Results The polymorphisms of TNFα,TNFβ,and IL-1β did not differ between the patients with ARDS and normals(P>0.05).The frequency of allele A2 of IL-1ra was 7.5% in normal,with an increase trend in ARDS(16.7%),however the polymorphism of IL-1ra did not differ between the patients with ARDS and normals(P>0.05).The frequency of allele 1 of TNFβ was 80% in the nonsurvivors,higher than in the survivors (P=0.017),with an odds ratio of 4.5.However,no differences were observed when the genotype of TNFα,TNFβ,IL-1β and IL-1ra between nonsurvivors and survivors were compared(P> 0.05).Conclusion No significant associations of TNFα,IL-1β and IL-1ra gene polymorphisms with susceptibility or outcome of ARDS were detected,allele 1 and allele 2 of TNFβ may have some role in determining the outcome of ARDS.