CTLA-4 genetic variants predict survival in patients with sepsis

Caspar Mewes, Benedikt Büttner, José Hinz, Ayelet Alpert, Aron Frederik Popov, Michael Ghadimi, Tim Beissbarth, Mladen Tzvetkov, Ole Jensen, Julius Runzheimer, Michael Quintel, Shai Shen-Orr, Ingo Bergmann, Ashham Mansur

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number70
JournalJournal of Clinical Medicine
Issue number1
StatePublished - Jan 2019


  • CTLA-4
  • Haplotypes
  • Predictors
  • Sepsis
  • Single nucleotide polymorphisms
  • Survival

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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