title: Association of genetic variation in chitotriosidase with atopy in Korean children.
abstract: BACKGROUND
  The atopic diseases, which are the most common chronic diseases of childhood, are complex genetic diseases that involve the contribution of multiple genetic factors to disease pathophysiology. Chitotriosidase is involved in innate immunity, but the association of chitotriosidase with allergic diseases remains unclear.
  
  
  OBJECTIVE
  To examine the contribution of genetic variation of the chitotriosidase-encoding gene CHIT1 to atopic phenotypes in a Korean cohort of children.
  
  
  METHODS
  We identified CHIT1 variations in a Korean population and conducted association analyses using 295 atopic and 242 nonatopic children. An independent replication study was performed using DNA samples from 148 atopic and 243 nonatopic children. All children were unrelated. We performed Western blot analysis in each genotype in vitro to see whether the CHIT1 A442G variation affects the final protein expression levels.
  
  
  RESULTS
  In the case-control association analysis, atopy was significantly associated with a single A442G (rs1065761) polymorphism in CHIT1 (odds ratio = 1.32, P = .01). Children with the c.442G risk allele had significantly higher blood eosinophils (P = .001), total serum IgE (P = .007), and eosinophil cationic protein (P = .02) levels. The results of the replication stage analysis confirmed a significant association between the A442G polymorphism and childhood atopy. The joint analysis of the exploratory and replication studies displayed a stronger significant association. The relative protein expression levels of chitotriosidase were significantly higher in both cell lysate and media with the G transfection compared with the wild type.
  
  
  CONCLUSIONS
  These results indicate that the nonsynonymous A442G polymorphism in CHIT1 is associated with risk of atopy.
authors.affiliation: Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Joonhee
authors.initials: J
authors.lastname: Park
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Hee Seon
authors.initials: HS
authors.lastname: Lee
authors.forename: Jaechun
authors.initials: J
authors.lastname: Lee
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Lee
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Hong
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Kim
authors.forename: Won Il
authors.initials: WI
authors.lastname: Heo
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Sohn
authors.forename: Kyu-Earn
authors.initials: KE
authors.lastname: Kim
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D047150:Eosinophil Cationic Protein / Q000097:blood; D004804:Eosinophils; D005260:Female; D023061:Gene Order; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006596:Hexosaminidases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea
chemical_list: D007073:Immunoglobulin E; D047150:Eosinophil Cationic Protein; D006596:Hexosaminidases; C086400:chitotriosidase