title: Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals.
abstract: Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (50-74 years old) who were immunized with inactivated TIV influenza vaccine that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r=0.23, p=0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p=0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine.
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, USA; Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, MN, USA.
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: White
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Beth R
authors.initials: BR
authors.lastname: Larrabee
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Grill
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, USA; Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jacobson
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, USA; Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, MN, USA; Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address: poland.gregory@mayo.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D056704:Adaptive Immunity; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D015992:Body Mass Index; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D020738:Leptin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000276:immunology / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D020738:Leptin; D053804:Granzymes
keywords: A/H1N1 virus; Adipocyte; BMI; Immune response; Immunosenescence; Influenza vaccine; Leptin; Obese; SNPs