Genes Immun. 2015 Apr 30. doi: 10.1038/gene.2015.12. [Epub ahead of print]
Genome-wide association study of IgG1 responses to the choline-binding protein PspC of Streptococcus pneumoniae.
Anderson D1, Fakiola M2, Hales BJ1, Pennell CE3, Thomas WR1, Blackwell JM1.
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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.Genes and Immunity advance online publication, 30 April 2015; doi:10.1038/gene.2015.12.
PMID: 25928883 [PubMed - as supplied by publisher]
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