VPS13D Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock.
J Innate Immun
; 7(5): 545-53, 2015.
Article
in En
| MEDLINE
| ID: mdl-25896417
ABSTRACT
BACKGROUND:
Genetic variations contribute to septic shock mortality. To discover a novel locus, we performed in vitro genome-wide association studies (GWAS) and further tested the result in a cohort of septic shock patients.METHODS:
Two in vitro GWAS using a quantitative trait locus analysis of stimulated IL-6 production in lymphoblastoid cells from 60 individuals of European ancestry were performed. VPS13D rs6685273 was genotyped in European ancestry patients (n = 498). The VPS13D gene was silenced in vitro.RESULTS:
Two GWAS using lymphoblastoid cells identified the locus of VPS13D rs6685273 that was significant in the same direction in both GWAS. The VPS13D rs6685273 C allele was associated with increased IL-6 production. Patients with septic shock who had the VPS13D rs6685273 CC genotype had an increased 28-day mortality (p = 0.023) and more organ failure (p < 0.05) compared to the CT/TT genotypes. VPS13D in vitro gene silencing in the HeLa cell line increased IL-6 production. Furthermore, the rs6685273 genotype was associated with differential VPS13D splice variant expression.CONCLUSIONS:
The VPS13D rs6685273 C allele was associated with increased IL-6 production in vitro. The patients with the VPS13D rs6685273 CC genotype had increased 28-day mortality and increased organ failure. VPS13D appears to regulate IL-6 production.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Shock, Septic
/
Lymphocytes
/
Proteins
/
Interleukin-6
Type of study:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
J Innate Immun
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2015
Document type:
Article
Affiliation country:
Canada