{"doi":"10.1159/000381265","title":"&lt;b&gt;&lt;i&gt;VPS13D&lt;/i&gt;&lt;/b&gt; Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock","abstract":"<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 gene was silenced in vitro.<h4>Results</h4>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.<h4>Conclusions</h4>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.","journal":"Journal of Innate Immunity","year":2015,"id":5666,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2015-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":52561,"name":"John H. Boyd","orcid":"0000-0002-3416-6362","position":1,"is_corresponding":false},{"id":52562,"name":"James A. Russell","orcid":"0000-0003-1484-7539","position":2,"is_corresponding":false},{"id":52563,"name":"Rosalía Aguirre-Hernández","orcid":null,"position":3,"is_corresponding":false},{"id":606,"name":"Mark D D. Wilkinson","orcid":"0000-0001-6960-357X","position":4,"is_corresponding":false},{"id":52564,"name":"Simone A. Thair","orcid":"0000-0002-2497-3945","position":5,"is_corresponding":false},{"id":52565,"name":"Emiri Nakada","orcid":null,"position":6,"is_corresponding":false},{"id":22202,"name":"Melissa K. McConechy","orcid":"0000-0002-1965-1095","position":7,"is_corresponding":false},{"id":52566,"name":"Christopher D. Fjell","orcid":"0000-0001-6304-2628","position":8,"is_corresponding":false},{"id":52567,"name":"Keith R. Walley","orcid":"0000-0003-4232-7266","position":9,"is_corresponding":false},{"id":52560,"name":"Taka‐aki Nakada","orcid":"0000-0002-4480-556X","position":10,"is_corresponding":false}],"reference_count":28,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}