Fang X M, Schröder S, Hoeft A, Stüber F
Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Germany.
Crit Care Med. 1999 Jul;27(7):1330-4. doi: 10.1097/00003246-199907000-00024.
To determine whether the allele frequencies and genotype distribution of an interleukin (IL)-1beta TaqI polymorphism and an interleukin-1 receptor antagonist polymorphism are associated with susceptibility to and outcome of severe sepsis. In addition, we analyze a possible linkage disequilibrium between a previously described NcoI polymorphism within the tumor necrosis factor (TNF) locus and the two IL-1 gene family polymorphisms.
Prospective, consecutive entry study of patients with diagnosis of severe sepsis.
Intensive care unit (ICU) of a university hospital.
Ninety-three patients with diagnosis of severe sepsis admitted to the ICU between June 1993 and June 1996.
None.
The polymorphic region within intron 2 of the IL-1ra gene containing variable numbers of a tandem repeat of 86 base pairs was amplified by means of the polymerase chain reaction. Alleles A1-5 are identified according to the size of the amplified DNA product. The region that contains the biallelic TaqI site within exon 5 of the IL-1beta gene was analyzed by polymerase chain reaction amplification and subsequent digestion using the TaqI restriction enzyme. A NcoI TNF-beta polymorphism was determined. The allele frequency of the allele IL-1raA2 was increased in 93 patients with severe sepsis compared with normal individuals (p < .01). No association with patients' outcome was observed. Allele frequencies or genotype distribution of the IL-1beta TaqI polymorphism did not differ between patients and controls. In addition, the allele TNFB2 of the NcoI TNF-beta polymorphism was associated with nonsurvival. Occurrence of the TNFB1 and TNFB2 alleles and genotypes was unrelated to alleles and genotypes of the two IL-1 gene family polymorphisms.
In contrast to the TNF-beta NcoI polymorphism, which has been associated with patients' nonsurvival, the allele IL-1raA2 of the polymorphism within the intron 2 of IL-1ra may contribute to susceptibility to sepsis.
确定白细胞介素（IL）-1β TaqI多态性和白细胞介素-1受体拮抗剂多态性的等位基因频率及基因型分布是否与严重脓毒症的易感性和预后相关。此外，我们分析肿瘤坏死因子（TNF）基因座内先前描述的NcoI多态性与两个IL-1基因家族多态性之间可能存在的连锁不平衡。
对诊断为严重脓毒症的患者进行前瞻性、连续入组研究。
大学医院重症监护病房（ICU）。
1993年6月至1996年6月间入住ICU的93例诊断为严重脓毒症的患者。
无。
通过聚合酶链反应扩增含86个碱基对串联重复可变数目的IL-1ra基因第2内含子内的多态性区域。根据扩增DNA产物的大小鉴定等位基因A1 - 5。通过聚合酶链反应扩增并随后使用TaqI限制性内切酶消化分析IL-1β基因第5外显子内包含双等位基因TaqI位点的区域。确定NcoI TNF-β多态性。与正常个体相比，93例严重脓毒症患者中IL-1raA2等位基因频率增加（p <.01）。未观察到与患者预后相关。患者和对照组之间IL-1β TaqI多态性的等位基因频率或基因型分布无差异。此外，NcoI TNF-β多态性的TNFB2等位基因与未存活相关。TNFB1和TNFB2等位基因及基因型的出现与两个IL-1基因家族多态性的等位基因和基因型无关。
与已被证明与患者未存活相关的TNF-β NcoI多态性不同，IL-1ra第2内含子内多态性的IL-1raA2等位基因可能促成脓毒症易感性。
