Format

Send to

Choose Destination
J Clin Med. 2019 Jan 10;8(1). pii: E70. doi: 10.3390/jcm8010070.

CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis.

Author information

1
Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany. caspar.mewes@med.uni-goettingen.de.
2
Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany. benedikt.buettner@med.uni-goettingen.de.
3
Department of Anesthesiology and Intensive Care Medicine, Klinikum Region Hannover, D-30459 Hannover, Germany. jose.hinz@krh.eu.
4
Faculty of Medicine, Technion⁻Israeli Institute of Technology, 31096 Haifa, Israel. ayelethappy@gmail.com.
5
Department of Thoracic and Cardiovascular Surgery, University Medical Center, Eberhard Karls University, D-72076 Tuebingen, Germany. aronf.popov@gmail.com.
6
Department of General and Visceral Surgery, University Medical Center, Georg August University, D-37075 Goettingen, Germany. mghadim@med.uni-goettingen.de.
7
Department of Medical Bioinformatics, University Medical Center, Georg August University, D-37077 Goettingen, Germany. tim.beissbarth@ams.med.uni-goettingen.de.
8
Department of Pharmacology, University Medical Center, Ernst-Moritz-Arndt-University, D-17487 Greifswald, Germany. mladen.tzvetkov@uni-greifswald.de.
9
Department of Clinical Pharmacology, University Medical Center, Georg August University, D-37075 Goettingen, Germany. ole.jensen@stud.uni-goettingen.de.
10
Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany. julius.runzheimer@med.uni-goettingen.de.
11
Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany. mquintel@med.uni-goettingen.de.
12
Faculty of Medicine, Technion⁻Israeli Institute of Technology, 31096 Haifa, Israel. shenorr@technion.ac.il.
13
Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany. ingo.bergmann@med.uni-goettingen.de.
14
Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany. ashham.mansur@med.uni-goettingen.de.

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.

KEYWORDS:

CTLA-4; haplotypes; predictors; sepsis; single nucleotide polymorphisms; survival

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center