CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis
AbstractCytotoxic 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
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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.
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. Journal of Clinical Medicine. 2019; 8(1):70.Chicago/Turabian Style
Mewes, Caspar; Büttner, Benedikt; Hinz, José; Alpert, Ayelet; Popov, Aron-Frederik; Ghadimi, Michael; Beissbarth, Tim; Tzvetkov, Mladen; Jensen, Ole; Runzheimer, Julius; Quintel, Michael; Shen-Orr, Shai; Bergmann, Ingo; Mansur, Ashham. 2019. "CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis." J. Clin. Med. 8, no. 1: 70.
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