Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury.

Abstract

To examine the influence of genetic variations in heat shock proteins on trauma outcome. Prospective, noninterventional, single-center study. Level I trauma center. Eighty consecutive severe multiple trauma patients. None. Plasma concentrations of interleukin-6 and tumor necrosis factor-alpha 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 with PstlI or NcoI, 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-alpha concentrations increased until day 5. Patients carrying the genotypes HSPA1B AG or HSPA1L CT had significantly higher plasma concentrations of tumor necrosis factor-alpha 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). The data indicate that genetic variations of the heat shock proteins HSPA1B and HSPA1L may contribute to clinical outcome after severe injury.