title: Filaggrin loss-of-function mutations are not a predisposing factor for atopic dermatitis in an Ishigaki Island under subtropical climate.
abstract: BACKGROUND
  Filaggrin (FLG) is a major protein component of the stratum corneum (SC) layer, and FLG loss-of-function mutations are a predisposing factor for atopic dermatitis (AD). Previous cohort studies of children from northern and western Europe have reported FLG loss-of-function mutation frequencies of 15.1-20.9% and 5.8-13.0% in AD and non-AD groups, respectively.
  
  
  OBJECTIVE
  To elucidate the association between AD prevalence of FLG loss-of-function mutation carriers and climate conditions, we determined the AD prevalence and FLG loss-of-function mutation frequencies in a cohort of children from Ishigaki Island. Ishigaki Island has a subtropical climate with high humidity (monthly average, 60.8-78.7%) and high temperature (monthly average, 18.5-29.4°C) throughout the year.
  
  
  METHODS
  We diagnosed AD prevalence and analyzed eight FLG loss-of-function mutations in the Japanese population against a cohort of 721 children from the Kyushu University Ishigaki Atopic Dermatitis Study (KIDS) cohort. Parents gave consent for the mutation analysis during their medical examinations from 2001 to 2006.
  
  
  RESULTS
  Average AD prevalence was 7.3% per year, and a total of 127 children (17.6%) were diagnosed with AD at least once between 2001 and 2006. The average total serum IgE level differed significantly between the AD and non-AD groups (199.0 and 69.0IU/ml, respectively). Although five kinds of FLG loss-of-function mutations isolated in previous Japanese FLG mutation studies were identified, the FLG loss-of-function mutation frequency in children of the KIDS cohort was not significantly different between the AD and non-AD groups (7.9% and 6.1%, respectively; P=0.174).
  
  
  CONCLUSIONS
  The FLG loss-of-function mutation frequency was not significantly different between the AD and non-AD groups in a cohort of children from Ishigaki Island, which has a subtropical climate, suggesting that FLG loss-of-function mutations are not always a predisposing factor for AD prevalence.
authors.affiliation: Center for Integrated Medical Research, Keio University School of Medicine, Tokyo, Japan; Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.affiliation: Laboratory of Gene Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Shiohama
authors.affiliation: Department of Dermatology, Kyushu University Hospital, Fukuoka, Japan. Electronic address: takeuchs@dermatol.med.kyushu-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeuchi
authors.affiliation: Department of Dermatology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakahara
authors.affiliation: Department of Dermatology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.affiliation: Laboratory for Respiratory and Allergic Diseases, Core for Genomic Medicine, Center for Integrative Medical Sciences, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Laboratory for Respiratory and Allergic Diseases, Core for Genomic Medicine, Center for Integrative Medical Sciences, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.affiliation: Advanced Research Center for Genome Super Power, Keio University, Tsukuba, Ibaraki, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ebihara
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.affiliation: Department of Dermatology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.affiliation: Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
authors.affiliation: Laboratory of Gene Medicine, Keio University School of Medicine, Tokyo, Japan; Advanced Research Center for Genome Super Power, Keio University, Tsukuba, Ibaraki, Japan. Electronic address: jkudoh@dmb.med.keio.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Kudoh
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000208:ethnology / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007249:Inflammation; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000502:physiology*; D007564:Japan; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D015995:Prevalence; D012867:Skin / Q000378:metabolism; D014329:Tropical Climate
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007073:Immunoglobulin E
keywords: Atopic dermatitis; Children cohort; FLG loss-of-function mutation; Ishigaki Island; Japanese