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Published on: December 10, 2013
Association of 17q12-q21 Asthma Risk Locus with Clinical Severity of Infant Respiratory Syncytial Virus Infection
Kedir N Turi1, Christopher McKennan2, Christian Rosas-Salazar3
1Department of Epidemiology and Biostatistics, Indiana University, 1025 E Seventh St., Bloomington, IN 47405, USA.
Insights
Genetic variations linked to childhood asthma also influence respiratory syncytial virus (RSV) infection severity and viral load. Specific gene variants in GSDMA and PGAP3 show associations with RSV outcomes, suggesting shared genetic pathways.
Area of Science:
- Genetics
- Immunology
- Pediatrics
Background:
- Childhood asthma is linked to genetic variations at the 17q12-q21 locus.
- Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory illness in infants.
- Understanding shared genetic factors between asthma and RSV could reveal novel therapeutic targets.
Purpose of the Study:
- To investigate if single nucleotide polymorphisms (SNPs) associated with childhood asthma at the 17q12-q21 locus are also associated with severe RSV infection and viral load.
- To identify specific genes within this locus that may influence RSV disease severity.
Main Methods:
- Candidate SNP association study in RSV-infected infants (INSPIRE cohort).
- Genotyping of nine SNPs at the 17q12-q21 locus.
- Evaluation of SNP association with RSV severity and viral load using an additive model.
- Replication analysis in a separate cohort (TCRI) of infants with severe RSV illness.
Main Results:
- An SNP (rs8069202-G) in the GSDMA gene was associated with increased RSV viral load and marginally with RSV severity in the INSPIRE cohort.
- An SNP (rs2941504) in the PGAP3 gene was associated with reduced risk of RSV severity.
- Associations were directionally replicated in the TCRI cohort, though not statistically significant (p < 0.05).
Conclusions:
- The GSDMA gene variant's association with RSV viral load and severity suggests a potential role in both conditions.
- Distinct pathways may link PGAP3 variants to asthma and severe RSV infection.
- Further research into these genetic links could inform strategies for managing both asthma and severe RSV.
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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