A Missense Genetic Variant in LRRC16A/CARMIL1 Improves Acute Respiratory Distress Syndrome Survival by Attenuating Platelet Count Decline

• DOI: 10.1164/rccm.201605-0946oc
• Publication Date: 2016-10-21T16:19:19Z
• Authors: Yongyue Wei; Paula Tejera; Zhaoxi Wang; Ruyang Zhang; Feng Chen; Li Su; Xihong Lin; Ednan K. Bajwa; B. Taylor Thompson; David C. Christiani
• Keywords: Male; 0301 basic medicine; Respiratory Distress Syndrome; Platelet Count; Microfilament Proteins; Mutation, Missense; Genetic Variation; Middle Aged; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Risk Factors; Humans; Female; Aged; Proportional Hazards Models

Rationale: Platelets are believed to contribute acute respiratory distress syndrome (ARDS) pathogenesis through inflammatory coagulation pathways. We recently reported that leucine-rich repeat–containing 16A (LRRC16A) modulates baseline platelet counts mediate ARDS risk.Objectives: To examine the role of LRRC16A in survival and its mediating effect platelets.Methods: A total 414 cases with from intensive care units (ICUs) were recruited who had exome-wide genotyping data, detailed counts, follow-up data during ICU hospitalization. Association single-nucleotide polymorphisms (SNPs) prognosis, SNPs analyzed. mRNA expression levels for 39 also evaluated.Measurements Main Results: Missense SNP rs9358856G>A within was associated favorable 28 days (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.38–0.87; P = 0.0084) 60 (P 0.0021) after admission. Patients carried variant genotype versus wild-type showed an attenuated count decline (∆PLT) (difference ∆PLT, −27.8; 0.025) ∆PLT outcomes. Mediation analysis indicated prognostic mediated (28-day survival: HRIndirect, 0.937; CI, 0.918−0.957; 0.0009, 11.53% effects mediated; 60-day 0.919; 0.901−0.936; 0.0001, 14.35% mediated). Functional exploration suggested this reduced at admission, which a lesser hospitalization.Conclusions: appears admission affect prognosis patients ARDS.