Dataset Information

VPS13D Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock.

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.

SUBMITTER: Nakada TA

PROVIDER: S-EPMC6738836 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

VPS13D Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock.

Nakada Taka-aki TA Boyd John H JH Russell James A JA Aguirre-Hernández Rosalía R Wilkinson Mark D MD Thair Simone A SA Nakada Emiri E McConechy Melissa K MK Fjell Christopher D CD Walley Keith R KR

Journal of innate immunity 20150417 5

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 25896417

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Dataset Information

VPS13D Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock.

Background

Methods

Results

Conclusions

Publications

VPS13D Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock.

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