Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury*
作者:
Ove Schröder,
Klaus-Martin Schulte,
Peter Ostermann,
Hans-Dietrich Röher,
Axel Ekkernkamp,
Reinhold Laun,
期刊:
Critical Care Medicine
(OVID Available online 2003)
卷期:
Volume 31,
issue 1
页码: 73-79
ISSN:0090-3493
年代: 2003
出版商: OVID
关键词: heat shock protein;multiple trauma;organ failure;polymorphism;cytokine;genotype;outcome;survival;inflammatory response;interleukin-6;tumor necrosis factor-&agr;;HSPA1B;HSPA1L
数据来源: OVID
摘要:
ObjectiveTo examine the influence of genetic variations in heat shock proteins on trauma outcome.DesignProspective, noninterventional, single-center study.SettingLevel I trauma center.SubjectsEighty consecutive severe multiple trauma patients.InterventionsNone.Measurements and Main ResultsPlasma concentrations of interleukin-6 and tumor necrosis factor-&agr; were measured over a 5-day course by chemiluminescence-immunoassay. The genotypes of the polymorphisms HSPA1B (HSP70-2) G1538A and HSPA1L (HSP70-Hom) C2437T were determined by polymerase chain reaction and restriction cleavage withPstI orNcoI, respectively. Allele frequency of the HSPA1B 1538 G allele was 0.569, and that of the HSPA1L 2437 T allele was 0.821. Interleukin-6 concentrations rapidly increased and dropped to almost normal after 5 days, whereas tumor necrosis factor-&agr; concentrations increased until day 5. Patients carrying the genotypes HSPA1B AG or HSPA1L CT had significantly higher plasma concentrations of tumor necrosis factor-&agr; and interleukin-6 compared with those with genotype GG or TT. Presence of the HSPA1L genotype CT also was a significant risk factor to develop liver failure (odds ratio, 4.6; 95% confidence interval, 1.5–14.1) and to acquire at least one complication severe enough to score three points according to the Denver multiple organ failure score (odds ratio, 3.0; 95% confidence interval, 1.1–9.2).ConclusionThe data indicate that genetic variations of the heat shock proteins HSPA1B and HSPA1L may contribute to clinical outcome after severe injury.
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