Severity of lung injury with respiratory syncytial virus (RSV) infection is variable and may be related to genetic variations. This preliminary report describes a prospective, family-based association study of children hospitalized secondary to RSV, aimed to determine whether intragenic and other haplotypes of surfactant proteins (SP)-A and SP-D are transmitted disproportionately from parents to offspring with RSV disease. Genomic DNA was genotyped for several SP-A and SP-D single nucleotide polymorphisms (SNPs). Transmission disequilibrium test analysis was used to determine transmission of variants and haplotypes from parents to affected offspring. Three hundred seventy-five individuals were studied, including 148 children with active RSV disease and one or both parents. The SP-A2 intragenic haplotype 1A2 was found to be protective (p = 0.013). The SP-D SNP DA160-A may possibly be an at-risk marker (p = 0.0058). Additional two-and three-marker haplotypes were associated with severe RSV disease, with two being protective (DA11-T/DA160-G and DA160-G/ SP-A2 1A0/SP-A1 6A2). We conclude that there may be associations between SP-A and SP-D and RSV disease. Further study is required to determine whether these variants can be used to target a high-risk patient population in clinical trials aimed at reducing either the symptoms of acute infection or long-term pulmonary sequelae.
All Science Journal Classification (ASJC) codes
- Pediatrics, Perinatology, and Child Health