Association of 17q12-q21 Asthma Risk Locus with Clinical Severity of Infant Respiratory Syncytial Virus Infection

17q12-q21哮喘风险位点与婴儿呼吸道合胞病毒感染临床严重程度的关联

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Abstract

This study examined whether SNPs at the 17q12-q21 locus that are associated with childhood asthma are also associated with severe respiratory syncytial virus (RSV) infection and viral load. We conducted a candidate SNP association study in the subset of RSV-infected infants who were parent-identified as White (n = 159) in the INSPIRE cohort. Nine SNPs at the 17q12-q21 locus were genotyped. We used an additive model to evaluate each SNP's association with RSV infection severity and viral load. Replication of significant associations was tested in the TCRI cohort: infants with severe RSV illness. In INSPIRE, an SNP rs8069202-G in the GSDMA gene was associated with increased RSV viral load (and marginally associated with RSV severity). SNP rs2941504, in the PGAP3 gene, was associated with a reduced risk of RSV severity. All significant associations were directionally replicated in the TCRI cohort but were insignificant at a p-value < 0.05. The association of a SNP in GSDMA with RSV viral load and RSV infection severity suggests that GSDMA may be contributing to both severe RSV infection and asthma development. On the other hand, the association between an SNP in PGAP3 and reduced RSV infection severity suggests distinct pathways link PGAP3 to these two respiratory outcomes.

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