Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus–Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination

• Published in: The Journal of infectious diseases Vol. 217; no. 4; pp. 560 - 566
• Main Authors: Voigt, Emily A, Haralambieva, Iana H, Larrabee, Beth L, Kennedy, Richard B, Ovsyannikova, Inna G, Schaid, Daniel J, Poland, Gregory A
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 30.01.2018
• Subjects: Major and Brief Reports; genetic; SNP; genome-wide association study; measles-mumps-rubella vaccine; rubella; immunity; rubella virus; polymorphisms; IL-6
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jix538

We conducted a genome-wide association study on 1843 subjects to identify genetic polymorphisms associated with cellular immunity after rubella vaccination. We identified single-nucleotide polymorphisms in the Wilms tumor gene WT1 that was significantly associated with interindividual differences in subject rubella-specific interleukin 6 secretion. Abstract Rubella vaccination induces widely variable immune responses in vaccine recipients. While rubella vaccination is effective at inducing immunity to rubella infection in most subjects, up to 5% of individuals do not achieve or maintain long-term protective immunity. To expand upon our previous work identifying genetic polymorphisms that are associated with these interindividual differences in humoral immunity to rubella virus, we performed a genome-wide association study in a large cohort of 1843 subjects to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus–specific cellular immune responses. We identified SNPs in the Wilms tumor protein gene (WT1) that were significantly associated (P < 5 × 10–8) with interindividual variations in rubella-specific interleukin 6 secretion from subjects’ peripheral blood mononuclear cells postvaccination. No SNPs were found to be significantly associated with variations in rubella-specific interferon-γ secretion. Our findings demonstrate that genetic polymorphisms in the WT1 gene in subjects of European ancestry are associated with interindividual differences in rubella virus–specific cellular immunity after measles-mumps-rubella II vaccination.