NDLI: Xanthine oxidoreductase gene polymorphisms are associated with high risk of sepsis and organ failure

Content Provider	Springer Nature : BioMed Central
Author	Gao, Li Rafaels, Nicholas Dudenkov, Tanda M. Damarla, Mahendra Damico, Rachel Maloney, James P. Moss, Marc Martin, Greg S. Sevransky, Jonathan Shanholtz, Carl Herr, Dan L. Garcia, Joe G.N. Hernandez-Beeftink, Tamara Villar, Jesús Flores, Carlos Beaty, Terri H. Brower, Roy Hassoun, Paul M. Barnes, Kathleen C.
Abstract	Background Sepsis and associated organ failures confer substantial morbidity and mortality. Xanthine oxidoreductase (XOR) is implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders including sepsis and sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether single nucleotide polymorphisms (SNPs) in the XDH gene (encoding XOR) might influence susceptibility to and outcome in patients with sepsis. Methods We genotyped 28 tag SNPs in XDH gene in the CELEG cohort, including 621 European American (EA) and 353 African American (AA) sepsis patients. Serum XOR activity was measured in a subset of CELEG subjects. Additionally, we assessed the functional effects of XDH variants utilizing empirical data from different integrated software tools and datasets. Results Among AA patients, six intronic variants (rs206805, rs513311, rs185925, rs561525, rs2163059, rs13387204), in a region enriched with regulatory elements, were associated with risk of sepsis (P < 0.008–0.049). Two out of six SNPs (rs561525 and rs2163059) were associated with risk of sepsis-associated ARDS in an independent validation cohort (GEN-SEP) of 590 sepsis patients of European descent. Two common SNPs (rs1884725 and rs4952085) in tight linkage disequilibrium (LD) provided strong evidence for association with increased levels of serum creatinine (Padjusted<0.0005 and 0.0006, respectively), suggesting a role in increased risk of renal dysfunction. In contrast, among EA ARDS patients, the missense variant rs17011368 (I703V) was associated with enhanced mortality at 60-days (P < 0.038). We found higher serum XOR activity in 143 sepsis patients (54.5 ± 57.1 mU/mL) compared to 31 controls (20.9 ± 12.4 mU/mL, P = 1.96 × 10− 13). XOR activity was associated with the lead variant rs185925 among AA sepsis patients with ARDS (P < 0.005 and Padjusted<0.01). Multifaceted functions of prioritized XDH variants, as suggested by various functional annotation tools, support their potential causality in sepsis. Conclusions Our findings suggest that XOR is a novel combined genetic and biochemical marker for risk and outcome in patients with sepsis and ARDS.
Related Links	https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-023-02481-8.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12931-023-02481-8
Journal	Respiratory Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2023-07-06
Access Restriction	Open
Subject Keyword	Pneumology Respiratory System Sepsis Acute respiratory distress syndrome Xanthine oxidoreductase Single nucleotide polymorphism Haplotype Biomarker Pneumology/Respiratory System
Content Type	Text
Resource Type	Article
Subject	Pulmonary and Respiratory Medicine
Journal Impact Factor	4.7/2023
5-Year Journal Impact Factor	5.3/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study

Risk stratification of patients with acute respiratory distress syndrome complicated with sepsis using lactate trajectories

IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

Risk factors for acute respiratory distress syndrome in sepsis patients: a retrospective study from a tertiary hospital in China

Interaction study of the effects of environmental exposure and gene polymorphisms of inflammatory and immune-active factors on chronic obstructive pulmonary disease

Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine

A prediction model for predicting the risk of acute respiratory distress syndrome in sepsis patients: a retrospective cohort study

Endocan as an early biomarker of severity in patients with acute respiratory distress syndrome

Xanthine oxidoreductase gene polymorphisms are associated with high risk of sepsis and organ failure

Similar Documents

Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study

Risk stratification of patients with acute respiratory distress syndrome complicated with sepsis using lactate trajectories

IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

Risk factors for acute respiratory distress syndrome in sepsis patients: a retrospective study from a tertiary hospital in China

Interaction study of the effects of environmental exposure and gene polymorphisms of inflammatory and immune-active factors on chronic obstructive pulmonary disease

Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine

A prediction model for predicting the risk of acute respiratory distress syndrome in sepsis patients: a retrospective cohort study

Endocan as an early biomarker of severity in patients with acute respiratory distress syndrome

Xanthine oxidoreductase gene polymorphisms are associated with high risk of sepsis and organ failure