Genetic Variation in IL18R1 and IL18 Genes and Inteferon gamma ELISPOT Response to Smallpox Vaccination: An Unexpected Relationship
JOURNAL OF INFECTIOUS DISEASES
Authors: Ovsyannikova, Inna G.; Haralambieva, Iana H.; Kennedy, Richard B.; O'Byrne, Megan M.; Pankratz, V. Shane; Poland, Gregory A.
Abstract
Background. Genetic association studies demonstrated a role for cytokine proteins and cytokine or cytokine receptor gene polymorphisms in smallpox vaccine-induced adaptive immunity. Methods. We examined the association of genetic polymorphisms with cellular (interferon [IFN] gamma enzyme-linked immunospot assay [ELISPOT]) immune response to smallpox vaccine in 1076 immunized individuals. Results. The majority of significant associations were discovered between single-nucleotide polymorphisms/haplotypes in IL18R1 and IL18 genes, in which we previously reported an association with vaccinia virus-induced neutralizing antibody titers in this study cohort. A functional coding IL18R1 polymorphism (rs1035130/Phe251 Phe; P = .01) was significantly associated with an allele dose-related increase in IFN-gamma production and was also associated with vaccinia-specific neutralizing antibody titers. Significant associations were also found between IL18R1 haplotypes and variations in IFN-gamma ELISPOT responses (global P < .0001). Conclusions. Our data suggest the importance of variants in the IL18R1 and IL18 genetic loci for broad-based smallpox vaccine-induced adaptive immunity.
Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population
NATURE GENETICS
Authors: Hirota, Tomomitsu; Takahashi, Atsushi; Kubo, Michiaki; Tsunoda, Tatsuhiko; Tomita, Kaori; Sakashita, Masafumi; Yamada, Takechiyo; Fujieda, Shigeharu; Tanaka, Shota; Doi, Satoru; Miyatake, Akihiko; Enomoto, Tadao; Nishiyama, Chiharu; Nakano, Nobuhiro; Maeda, Keiko; Okumura, Ko; Ogawa, Hideoki; Ikeda, Shigaku; Noguchi, Emiko; Sakamoto, Tohru; Hizawa, Nobuyuki; Ebe, Koji; Saeki, Hidehisa; Sasaki, Takashi; Ebihara, Tamotsu; Amagai, Masayuki; Takeuchi, Satoshi; Furue, Masutaka; Nakamura, Yusuke; Tamari, Mayumi
Abstract
Atopic dermatitis is a common inflammatory skin disease caused by interaction of genetic and environmental factors. On the basis of data from a genome-wide association study (GWAS) and a validation study comprising a total of 3,328 subjects with atopic dermatitis and 14,992 controls in the Japanese population, we report here 8 new susceptibility loci: IL1RL1-IL18R1-IL18RAP (P-combined = 8.36 x 10(-18)), the major histocompatibility complex (MHC) region (P = 8.38 x 10(-20)), OR10A3-NLRP10 (P = 1.54 x 10(-22)), GLB1 (P = 2.77 x 10(-16)), CCDC80 (P = 1.56 x 10(-19)), CARD11 (P = 7.83 x ZNF365 (P = 5.85 x 10(-20)) and CYP24A1-PFDN4 (P = 1.65 x 10(-8)). We also replicated the associations of the FLG, C11orf30, TMEM232-SLC25A46, TNFRSF6B-ZGPAT, OVOL1, ACTL9 and KIF3A-IL13 loci that were previously reported in GWAS of European and Chinese individuals and a meta-analysis of GWAS for atopic dermatitis. These findings advance the understanding of the genetic basis of atopic dermatitis.
COA
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