Schroeder S, Reck M, Hoeft A, Stüber F
Klinik und Poliklinik für Anästhesiologie und Spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, Germany.
Crit Care Med. 1999 Jul;27(7):1265-70. doi: 10.1097/00003246-199907000-00006.
To determine whether the genotype and allelic frequencies of two human leukocyte antigen-linked bi-allelic 70-kilodalton heat shock protein (HSP70) gene polymorphisms are associated with susceptibility to and outcome of severe sepsis. Furthermore, we investigated a possible linkage between HSP70 gene polymorphisms and the previously reported and mortality-related tumor necrosis factor-beta (TNF-beta) NcoI gene polymorphism.
Consecutive entry study of patients with severe sepsis.
Surgical intensive care unit in a university hospital.
Eighty-seven patients with a diagnosis of severe sepsis.
None.
We studied two bi-allelic polymorphisms within the coding region of the constitutively expressed HSP70-HOM C/T, and the stress-inducible HSP70-2 G/A in patients with severe sepsis. The HSP70-HOM Ncol, HSP70-2 Pstl, and TNF-beta NcoI polymorphisms were identified by means of the polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. No significant differences in genotype and allelic frequencies were observed for both HSP70 gene polymorphisms between the 87 patients and the 110 healthy Caucasians serving as the control group. In addition, no differences in genotype and allelic frequencies between surviving and nonsurviving patients were detected. The allelic frequencies in the group of nonsurvivors were 0.8 for the HSP70-HOM C allele and 0.2 for the HSP70-HOM T allele vs. 0.87 and 0.13 for the survivors (p > .05). The frequency for the HSP70-2 G allele was 0.36 and 0.64 for the HSP70-2 A allele in the group of nonsurvivors vs. 0.41 and 0.59 for the survivors (p > .05). Analysis of a possible linkage between HSP70 and TNF-beta genotypes resulted in a significant association (odds ratio, 4.15; p < .01) of the HSP70-2 A/A homozygous genotype and the TNFB2/B2 homozygous genotype, which is reported to be a genomic marker for a poor prognosis in severe sepsis.
Our data show that the bi-allelic NcoI and PstI polymorphisms within the HSP70-HOM and HSP70-2 locus, respectively, are associated with neither susceptibility to nor outcome of severe sepsis. Moreover, we found a linkage between HSP70-2 A homozygotes and the previously reported and mortality-related homozygous genotype, TNFB2/B2, in patients suffering from severe sepsis.
确定两个人类白细胞抗原相关的双等位基因70千道尔顿热休克蛋白（HSP70）基因多态性的基因型和等位基因频率是否与严重脓毒症的易感性及预后相关。此外，我们研究了HSP70基因多态性与先前报道的、与死亡率相关的肿瘤坏死因子-β（TNF-β）NcoI基因多态性之间的可能联系。
对严重脓毒症患者进行连续入组研究。
大学医院的外科重症监护病房。
87例诊断为严重脓毒症的患者。
无。
我们研究了组成型表达的HSP70-HOM C/T编码区域内的两个双等位基因多态性，以及严重脓毒症患者中应激诱导型HSP70-2 G/A。通过聚合酶链反应及随后对聚合酶链反应产物进行限制性分析来鉴定HSP70-HOM Ncol、HSP70-2 Pstl和TNF-β NcoI多态性。在87例患者与作为对照组的110例健康白种人之间，未观察到两种HSP70基因多态性在基因型和等位基因频率上有显著差异。此外，在存活患者和未存活患者之间未检测到基因型和等位基因频率的差异。未存活患者组中HSP70-HOM C等位基因的频率为0.8，HSP70-HOM T等位基因的频率为0.2，而存活患者分别为0.87和0.13（p>.05）。未存活患者组中HSP70-2 G等位基因的频率为0.36，HSP70-2 A等位基因的频率为0.64，而存活患者分别为0.41和0.59（p>.05）。对HSP70和TNF-β基因型之间可能联系的分析显示，HSP70-2 A/A纯合基因型与TNFB2/B2纯合基因型之间存在显著关联（优势比，4.15；p<.01），据报道TNFB2/B2纯合基因型是严重脓毒症预后不良的基因组标志物。
我们的数据表明，HSP70-HOM和HSP70-2基因座内的双等位基因NcoI和PstI多态性分别与严重脓毒症的易感性及预后均无关。此外，我们发现严重脓毒症患者中HSP70-2 A纯合子与先前报道的、与死亡率相关的纯合基因型TNFB2/B2之间存在联系。
