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J. Clin. Med. 2019, 8(1), 70; https://doi.org/10.3390/jcm8010070

CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis

1
Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany
2
Department of Anesthesiology and Intensive Care Medicine, Klinikum Region Hannover, D-30459 Hannover, Germany
3
Faculty of Medicine, Technion–Israeli Institute of Technology, 31096 Haifa, Israel
4
Department of Thoracic and Cardiovascular Surgery, University Medical Center, Eberhard Karls University, D-72076 Tuebingen, Germany
5
Department of General and Visceral Surgery, University Medical Center, Georg August University, D-37075 Goettingen, Germany
6
Department of Medical Bioinformatics, University Medical Center, Georg August University, D-37077 Goettingen, Germany
7
Department of Pharmacology, University Medical Center, Ernst-Moritz-Arndt-University, D-17487 Greifswald, Germany
8
Department of Clinical Pharmacology, University Medical Center, Georg August University, D-37075 Goettingen, Germany
These authors contributed equally.
*
Author to whom correspondence should be addressed.
Received: 13 December 2018 / Revised: 26 December 2018 / Accepted: 7 January 2019 / Published: 10 January 2019
(This article belongs to the Section Hematology)
Full-Text   |   PDF [1308 KB, uploaded 10 January 2019]   |  

Abstract

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a coinhibitory checkpoint protein expressed on the surface of T cells. A recent study by our working group revealed that the rs231775 single nucleotide polymorphism (SNP) in the CTLA-4 gene was associated with the survival of patients with sepsis and served as an independent prognostic variable. To further investigate the impact of CTLA-4 genetic variants on sepsis survival, we examined the effect of two functional SNPs, CTLA-4 rs733618 and CTLA-4 rs3087243, and inferred haplotypes, on the survival of 644 prospectively enrolled septic patients. Kaplan–Meier survival analysis revealed significantly lower 90-day mortality for rs3087243 G allele carriers (n = 502) than for AA-homozygous (n = 142) patients (27.3% vs. 40.8%, p = 0.0024). Likewise, lower 90-day mortality was observed for TAA haplotype-negative patients (n = 197; compound rs733618 T/rs231775 A/rs3087243 A) than for patients carrying the TAA haplotype (n = 447; 24.4% vs. 32.9%, p = 0.0265). Carrying the rs3087243 G allele hazard ratio (HR): 0.667; 95% confidence interval (CI): 0.489–0.909; p = 0.0103) or not carrying the TAA haplotype (HR: 0.685; 95% CI: 0.491–0.956; p = 0.0262) remained significant covariates for 90-day survival in the multivariate Cox regression analysis and thus served as independent prognostic variables. In conclusion, our findings underscore the significance of CTLA-4 genetic variants as predictors of survival of patients with sepsis. View Full-Text
Keywords: sepsis; CTLA-4; single nucleotide polymorphisms; haplotypes; survival; predictors sepsis; CTLA-4; single nucleotide polymorphisms; haplotypes; survival; predictors
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Mewes, C.; Büttner, B.; Hinz, J.; Alpert, A.; Popov, A.-F.; Ghadimi, M.; Beissbarth, T.; Tzvetkov, M.; Jensen, O.; Runzheimer, J.; Quintel, M.; Shen-Orr, S.; Bergmann, I.; Mansur, A. CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis. J. Clin. Med. 2019, 8, 70.

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