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摘要
Rationale: 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. @@@ Objectives: To examine the role of LRRC16A in ARDS survival and its mediating effect through platelets. @@@ Methods: 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. @@@ Measurements and Main Results: Missense SNP rs9358856G>A 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 (Delta PLT) within 28 days (difference of Delta PLT, -27.8; P = 0.025) after ICU admission. Patients with Delta PLT were associated with favorable ARDS outcomes. Mediation analysis indicated that the SNP prognostic effect was mediated through APLT within 28 days (28-day survival: HRIndirect, 0.937; 95% CI, 0.918-0.957; P = 0.0009, 11.53% effects mediated; 60-day survival: HRIndirect, 0.919; 95% CI, 0.901-0.936; P = 0.0001, 14.35% effects mediated). Functional exploration suggested that this SNP reduced LRRC16A expression at ICU admission, which was associated with a lesser APLT during ICU hospitalization. @@@ Conclusions: LRRC16A appears to mediate APLT after ICU admission to affect the prognosis in patients with ARDS.
- 出版日期2017-5-15
- 单位南京医科大学
