Document Detail


IL1RN coding variant is associated with lower risk of acute respiratory distress syndrome and increased plasma IL-1 receptor antagonist.
MedLine Citation:
PMID:  23449693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Acute respiratory distress syndrome (ARDS) behaves as a complex genetic trait, yet knowledge of genetic susceptibility factors remains incomplete.
OBJECTIVES: To identify genetic risk variants for ARDS using large scale genotyping.
METHODS: A multistage genetic association study was conducted of three critically ill populations phenotyped for ARDS. Stage I, a trauma cohort study (n = 224), was genotyped with a 50K gene-centric single-nucleotide polymorphism (SNP) array. We tested SNPs associated with ARDS at P < 5 × 10(-4) for replication in stage II, a trauma case-control population (n = 778). SNPs replicating their association in stage II (P < 0.005) were tested in a stage III nested case-control population of mixed subjects in the intensive care unit (n = 2,063). Logistic regression was used to adjust for potential clinical confounders. We performed ELISA to test for an association between ARDS-associated genotype and plasma protein levels.
MEASUREMENTS AND MAIN RESULTS: A total of 12 SNPs met the stage I threshold for an association with ARDS. rs315952 in the IL1RN gene encoding IL-1 receptor antagonist (IL1RA) replicated its association with reduced ARDS risk in stages II (P < 0.004) and III (P < 0.02), and was robust to clinical adjustment (combined odds ratio = 0.81; P = 4.2 × 10(-5)). Plasma IL1RA level was associated with rs315952C in a subset of critically ill subjects. The effect of rs315952 was independent from the tandem repeat variant in IL1RN.
CONCLUSIONS: The IL1RN SNP rs315952C is associated with decreased risk of ARDS in three populations with heterogeneous ARDS risk factors, and with increased plasma IL1RA response. IL1RA may attenuate ARDS risk.
Authors:
Nuala J Meyer; Rui Feng; Mingyao Li; Yang Zhao; Chau-Chyun Sheu; Paula Tejera; Robert Gallop; Scarlett Bellamy; Melanie Rushefski; Paul N Lanken; Richard Aplenc; Grant E O'Keefe; Mark M Wurfel; David C Christiani; Jason D Christie
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  187     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-02     Completed Date:  2013-06-27     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  950-9     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Case-Control Studies
Cohort Studies
Enzyme-Linked Immunosorbent Assay
Female
Genetic Association Studies
Genetic Predisposition to Disease*
Genotype
Humans
Intensive Care Units
Logistic Models
Male
Middle Aged
Polymorphism, Single Nucleotide
Receptors, Interleukin-1 / antagonists & inhibitors,  blood,  genetics*
Respiratory Distress Syndrome, Adult / blood,  genetics*,  physiopathology
Risk
Risk Factors
Severity of Illness Index
Grant Support
ID/Acronym/Agency:
GM066946/GM/NIGMS NIH HHS; HL060290/HL/NHLBI NIH HHS; HL060710/HL/NHLBI NIH HHS; HL079063/HL/NHLBI NIH HHS; HL081619/HL/NHLBI NIH HHS; HL090021/HL/NHLBI NIH HHS; HL102254/HL/NHLBI NIH HHS; K23 HL102254/HL/NHLBI NIH HHS; L30 HL097857/HL/NHLBI NIH HHS; RC2HL101770/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Interleukin-1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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