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Neutrophil GM-CSF signaling in inflammatory bowel disease patients is influenced by non-coding genetic variants.

ABSTRACT: Neutrophil dysfunction and GM-CSF auto-antibodies are observed in pediatric and adult patients with Crohn's disease (CD). We associated damaging coding variants with low GM-CSF induced STAT5 stimulation index (GMSI) in pediatric CD patients and implicated variation of neutrophil GM-CSF signaling in cell function and disease complications. Because many CD patients with low GMSI do not carry damaging coding mutations, we sought to test the hypothesis that non-coding variants contribute to this phenotype. We enrolled, performed whole genome sequencing, and measured the GMSI in 77 CD and ulcerative colitis (UC) patients (24 low and 53 normal GMSI). We identified 4 non-coding variants (rs3808851, rs10974787, rs10974788 and rs10974789) in RCL1 significantly associated with variation of GMSI level (p?

SUBMITTER: Venkateswaran S

PROVIDER: S-EPMC6591305 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Neutrophil GM-CSF signaling in inflammatory bowel disease patients is influenced by non-coding genetic variants.

Venkateswaran Suresh S Denson Lee A LA Jurickova Ingrid I Dodd Anne A Zwick Michael E ME Cutler David J DJ Kugathasan Subra S Okou David T DT

Scientific reports 20190624 1

Neutrophil dysfunction and GM-CSF auto-antibodies are observed in pediatric and adult patients with Crohn's disease (CD). We associated damaging coding variants with low GM-CSF induced STAT5 stimulation index (GMSI) in pediatric CD patients and implicated variation of neutrophil GM-CSF signaling in cell function and disease complications. Because many CD patients with low GMSI do not carry damaging coding mutations, we sought to test the hypothesis that non-coding variants contribute to this phe ...[more]

PMID: 31235766

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