title: Staphylococcus aureus enterotoxin sensitization involvement and its association with the CysLTR1 variant in different asthma phenotypes.
abstract: BACKGROUND
  Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain.
  
  
  OBJECTIVE
  To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene (CysLTR1), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma.
  
  
  METHODS
  We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner.
  
  
  RESULTS
  A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset.
  
  
  CONCLUSIONS
  SE sensitization contributes to TH2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Kinki Hokuriku Airway Disease Conference, Osaka, Japan. Electronic address: hmatsumo@kuhp.kyoto-u.ac.jp.
authors.forename: Hisako
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Kinki Hokuriku Airway Disease Conference, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kanemitsu
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Kinki Hokuriku Airway Disease Conference, Osaka, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Nagasaki
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Medicine and Allergology, Faculty of Medicine, Kinki University, Osaka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tohda
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Internal Medicine, Fujita Health University Second Educational Hospital, Aichi, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Horiguchi
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Medicine, Takatsuki Red Cross Hospital, Osaka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kita
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Internal Medicine, Fujita Health University Second Educational Hospital, Aichi, Japan.
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Kuwabara
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Otsuka
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimura
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ohkura
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Medicine and Allergology, Faculty of Medicine, Kinki University, Osaka, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Hematology and Respiratory Medicine, Kochi University, Kochi, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Hematology and Respiratory Medicine, Kochi University, Kochi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oguma
authors.affiliation: Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Hiroshima Allergy and Respiratory Clinic, Hiroshima, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Hozawa
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Izuhara
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Ito
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Kinki Hokuriku Airway Disease Conference, Osaka, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oguma
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tajiri
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Shino-Test Corporation, Kanagawa, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ono
authors.affiliation: Department of Laboratory Medicine, Saga Medical School, Saga, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Laboratory for Respiratory and Allergic Diseases, Core for Genomic Medicine, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research, Yokohama, Kanagawa, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Center for Genomic Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Laboratory for Respiratory and Allergic Diseases, Core for Genomic Medicine, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research, Yokohama, Kanagawa, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.affiliation: Department of Health Promotion, National Institute of Public Health, Wako, Saitama, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Center for Genomic Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.affiliation: Center for Genomic Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Kinki Hokuriku Airway Disease Conference, Osaka, Japan; Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University School of Medical Sciences, Aichi, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Kinki Hokuriku Airway Disease Conference, Osaka, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000368:Aged; D000483:Alleles; D001249:Asthma / Q000175:diagnosis* / Q000209:etiology* / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D004198:Disease Susceptibility; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018077:Receptors, Leukotriene / Q000235:genetics* / Q000378:metabolism; D012129:Respiratory Function Tests; D012307:Risk Factors; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D015415:Biomarkers; D004768:Enterotoxins; D018077:Receptors, Leukotriene; D007073:Immunoglobulin E; C083169:leukotriene D4 receptor