A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.

摘要: SummaryBackground Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and responsiveness to corticosteroids asthmatics. Objective We sought identify adults genetic determinants of fractional exhaled levels assess whether environmental disease-related factors influence these associations. Methods We performed genome-wide association study FeNO through meta-analysis two independent discovery samples European ancestry: outbred EGEA (French Epidemiological on Genetics Environment Asthma, N = 610 adults) Hutterites (N = 601 adults), founder population living communal farms. Replication main findings was assessed from an isolated village Sardinia (Talana study, N = 450). We then investigated asthma, atopy tobacco smoke exposure associations, they were also associated with values children EAGLE (EArly & Lifecourse Epidemiology, N = 8858) consortium. Results We detected common variant RAB27A (rs2444043) that reached significant level (P = 1.6 × 10−7) combined replication adult data sets. This SNP belongs member RAS oncogene family (RAB27A) expression quantitative trait locus lymphoblastoid cell lines asthmatics. A second suggestive (rs2194437, P = 8.9 × 10−7) located nearby sodium/calcium exchanger 1 (SLC8A1) mainly atopic subjects influenced by inhaled corticosteroid use. These loci not childhood values. Conclusions Clinical Relevance This identified gene influencing specifically biological relevance regulation levels. provides new insight into mechanisms underlying adults.