Genome-Wide Determinants of Cellular Immune Responses to Mumps Vaccine.

BACKGROUND

We have previously described genetic polymorphisms in candidate genes that are associated with inter-individual variations in antibody responses to mumps vaccination. To expand upon our previous work, we performed a genome-wide association study (GWAS) to discover host genetic variants associated with mumps vaccine-induced cellular immune responses.

METHODS

We performed a GWAS of mumps-specific immune response outcomes (11 secreted cytokines/chemokines) in a cohort of 1,406 subjects.

RESULTS

Among the 11 cytokine/chemokines we studied, four (IFN-γ, IL-2, IL-1β, and TNFα) demonstrated GWAS signals reaching genome-wide significance (p<5 x 10 -8 ). A genomic region (encoding Sialic acid-binding immunoglobulin-type lectins/SIGLEC) located on chromosome 19q13 (p<5×10 -8 ) was associated with both IL-1β and TNFα responses. The SIGLEC5/SIGLEC14 region contained 11 statistically significant single nucleotide polymorphisms (SNPs), including the intronic SIGLEC5 rs872629 (p=1.3E-11) and rs1106476 (p=1.32E-11) whose alternate alleles were significantly associated with decreased levels of mumps-specific IL-1β (rs872629, p=1.77E-09; rs1106476, p=1.78E-09) and TNFα (rs872629, p=1.3E-11; rs1106476, p=1.32E-11) production.

CONCLUSIONS

Our results suggest that SNPs in the SIGLEC5/SIGLEC14 genes play a role in cellular and inflammatory immune responses to mumps vaccination. These findings motivate further research into the functional roles of SIGLEC genes in the regulation of mumps vaccine-induced immunity.