Associations between cytokine/cytokine receptor single nucleotide polymorphisms and humoral immunity to measles, mumps and rubella in a Somali population

Abstract

We genotyped a Somali population (n=85; age ≤ 30 years) for 617 cytokine and cytokine receptor SNPs using Illumina GoldenGate genotyping to determine associations with measles, mumps and rubella immunity. Overall, sixty-one significant associations (p≤0.01) were found between SNPs belonging to cytokine receptor genes regulating Th1 (IL12RB2, IL2RA and B) and Th2 (IL4R, IL10RB) immunity, and cytokine (IL1B, TNFA, IL6 and IFNB1) and cytokine receptor (IL1RA, IFNAR2, IL18R1, TNFRSF1A and B) genes regulating innate immunity, and variations in antibody levels to measles, mumps or rubella. SNPs within two major inflammatory cytokine genes, TNFA and IL6, demonstrated associations with measles-specific antibodies. Specifically, the minor allele variant of rs1799964 (TNFA -1211 C>T) was associated with primarily seronegative values (median EIA index values ≤0.87; p=0.002; q=0.23) in response to measles disease and/or vaccination. A heterozygous variant CT for rs2069849 (IL6 +4272C>T; Phe201Phe) was also associated with seronegative values and a lower median level of antibody response to measles disease and/or vaccination (p=0.004; q=0.36) or measles vaccination alone (p=0.008). Several SNPs within the coding and regulatory regions of cytokine and cytokine receptor genes demonstrated associations with mumps and rubella antibody levels, but were less informative as strong LD patterns and lower frequencies for minor alleles were observed among these SNPs. Our study identifies specific SNPs in innate immune response genes that may play a role in modulating antibody responses to measles vaccination and/or infection in Somali subjects.

Genetic polymorphisms associated with rubella virus-specific cellular immunity following MMR vaccination

“…We have previously identified a number of genetic variants (mainly HLA alleles and SNPs) associated with variations in cellular and/or humoral immunity to rubella vaccine. (Dhiman et al 2010a; Dhiman et al 2008; Haralambieva et al 2010; Jacobson et al 2009; Kennedy et al 2010; Ovsyannikova et al 2010b; Ovsyannikova et al 2004, 2005; Ovsyannikova et al 2009a; Ovsyannikova et al 2006; Ovsyannikova et al 2009b; Ovsyannikova et al 2010c; Pankratz et al 2010) Our current study design incorporates several important elements: the use of SNP data to define race/ethnicity, and the inclusion of two separate cohorts for SNP discovery and replication. Our study also has several limitations that include: the chance for rubella exposure and/or disease in our San Diego cohort; relatively small cohort sizes (especially when compared to cancer gene association studies with tens of thousands of subjects); and response outcomes that reflect complex immunologic processes controlled by multiple genes and pathways, where individual SNPs have minor contributions to the spectrum of immune response.…”

“…Homozygous A and heterozygous individuals had median IFNγ secretion levels of ~ 6pg/ml. Two of the SNPs were located near the IL10RB gene and genetic polymorphisms in this region have also been associated with chronic hepatitis B infection,(Romporn et al 2013) cytokine responses to smallpox vaccine,(Ovsyannikova et al 2012a) HIV infection outcomes,(Shrestha et al 2010) immune responses following MMR vaccination,(Dhiman et al 2008) and malaria susceptibility. (Khor et al 2007)…”

Race and sex-based differences in cytokine immune responses to smallpox vaccine in healthy individuals

“…Sex-based differences in vaccine efficacy, adverse events, and humoral immune response after immunization have been reported for many viral vaccines, including measles-mumps-rubella (MMR), influenza, hepatitis A, hepatitis B, yellow fever, smallpox, rabies and human papillomavirus. [12] In most cases, women generate a more robust antibody response to vaccines than men, while data on sex-based differences in cellular immune responses remains controversial [6,9,12–19]. The effects of race and ethnicity on variations in vaccine-induced immunity, including cellular immunity, have not been comprehensively studied.…”

Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients

“…(Dhiman et al 2010a; Dhiman et al 2008; Haralambieva et al 2010; Ovsyannikova et al 2010a; Ovsyannikova et al 2010b; Ovsyannikova et al 2004; Ovsyannikova et al 2005) In this report, we conducted genome-wide SNP typing in order to perform the corresponding genetic association analyses in a manner that enabled the discovery of potentially novel associations throughout the genome.…”