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- Title
Genome-wide association study of IgG1 responses to the choline-binding protein PspC of Streptococcus pneumoniae.
- Authors
Anderson, D; Fakiola, M; Hales, B J; Pennell, C E; Thomas, W R; Blackwell, J M
- Abstract
Streptococcus pneumoniae causes invasive pneumococcal disease. Delayed development of antibodies to S. pneumoniae in infancy is associated with the development of atopy and asthma. Pneumococcal surface protein C (PspC) is a vaccine candidate and variation in its choline-binding region is associated with invasive disease. This study examined 523 060 single-nucleotide polymorphisms in The Western Australian Pregnancy Cohort (Raine) Study to find loci influencing immunoglobulin G1 (IgG1) responses to PspC measured at age 14 years (n=1152). Genome-wide significance (top SNP rs9275596; P=3.1 × 10−14) was only observed at human leucocyte antigen (HLA). Imputed HLA amino-acid polymorphisms showed the strongest associations at positions DRB1 47 (P=3.2 × 10−11), 13SRG (P=9.8 × 10-10) and 11SP (P=9.8 × 10−10), and at DQA1 34 (P=6.4 × 10-10), DQB1 167R (P=9.3 × 10−6) and HLA-B 95 W (P=1.2 × 10−9). Conditional analyses showed independent contributions from DRB1 47 and DQB1 167R to the signal at rs9275596, supported by an omnibus test showing a strong signal for the haplotype DRB1_47_DQB1_167 (P=9.02 × 10−15). In silico analysis showed that DRB1 four-digit allele groups defined by DRB1 47F bind to a greater complexity of core 9-mer epitopes compared with DRB1 47Y, especially across repeats in the C-term choline-binding region. Consequent differences in CD4 T-cell help for IgG1 to PspC could have implications for vaccine design. Further analysis in other cohorts is merited.
- Subjects
STREPTOCOCCUS pneumoniae; IMMUNOGLOBULIN G; CARRIER proteins; BACTERIAL disease treatment; CHOLINE; PNEUMOCOCCAL surface protein A; SINGLE nucleotide polymorphisms; COHORT analysis
- Publication
Genes & Immunity, 2015, Vol 16, Issue 5, p289
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/gene.2015.12