A Missense Genetic Variant in LRRC16A/CARMIL1 Improves Acute Respiratory Distress Syndrome Survival by Attenuating Platelet Count Decline
| Autor: | B. T. Thompson, Feng Chen, Zhaoxi Wang, Paula Tejera, Ruyang Zhang, Wei Y, Li Su, David C. Christiani, Ednan K. Bajwa, Xihong Lin |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty ARDS Mutation Missense Single-nucleotide polymorphism Critical Care and Intensive Care Medicine Polymorphism Single Nucleotide Gastroenterology Pathogenesis 03 medical and health sciences 0302 clinical medicine Risk Factors Intensive care Internal medicine medicine Humans SNP Platelet 030212 general & internal medicine Intensive care medicine Aged Proportional Hazards Models Respiratory Distress Syndrome Platelet Count Proportional hazards model business.industry Microfilament Proteins Hazard ratio Editorials Genetic Variation Middle Aged medicine.disease 030228 respiratory system Female business |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 195:1353-1361 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.201605-0946oc |
| Popis: | Platelets are believed to contribute to acute respiratory distress syndrome (ARDS) pathogenesis through inflammatory coagulation pathways. We recently reported that leucine-rich repeat-containing 16A (LRRC16A) modulates baseline platelet counts to mediate ARDS risk.To examine the role of LRRC16A in ARDS survival and its mediating effect through platelets.A total of 414 cases with ARDS from intensive care units (ICUs) were recruited who had exome-wide genotyping data, detailed platelet counts, and follow-up data during ICU hospitalization. Association of LRRC16A single-nucleotide polymorphisms (SNPs) and ARDS prognosis, and the mediating effect of SNPs through platelet counts were analyzed. LRRC16A mRNA expression levels for 39 cases with ARDS were also evaluated.Missense SNP rs9358856GA within LRRC16A was associated with favorable survival within 28 days (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.38-0.87; P = 0.0084) and 60 days (P = 0.0021) after ICU admission. Patients with ARDS who carried the variant genotype versus the wild-type genotype showed an attenuated platelet count decline (∆PLT) within 28 days (difference of ∆PLT, -27.8; P = 0.025) after ICU admission. Patients with ∆PLT were associated with favorable ARDS outcomes. Mediation analysis indicated that the SNP prognostic effect was mediated through ∆PLT within 28 days (28-day survival: HRLRRC16A appears to mediate ∆PLT after ICU admission to affect the prognosis in patients with ARDS. |
| Databáze: | OpenAIRE |
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