title: Genetic effect of CCR3 and IL5RA gene polymorphisms on eosinophilia in asthmatic patients.
abstract: BACKGROUND
  Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophil-specific cytokines and chemokines and their receptors.
  
  
  OBJECTIVE
  We investigated the association of polymorphisms in CCR3 and IL5RA with asthma susceptibility or peripheral blood eosinophilia and the effects of the polymorphisms on receptor expression.
  
  
  METHODS
  Polymorphisms in CCR3 and IL5RA were identified and genotyped in 576 asthmatic patients and 180 healthy control subjects. CCR3 and IL-5 receptor alpha (IL-5R alpha) protein expression on eosinophils was measured by means of flow cytometry.
  
  
  RESULTS
  Although polymorphisms in CCR3 were not associated with asthma susceptibility, the CCR3 haplotype ht2 showed a negative gene dose effect on the eosinophil count (P = .003-.009). IL5RA c.-5091G>A was weakly associated with eosinophil count. The effects of ht2 were greater when paired with IL5RA c.-5091A (P = .001-.002). CCR3 protein expression was higher on eosinophils of asthmatic patients without ht2 than in those with ht2. Asthmatic patients with the IL5RA c.-5091A allele showed higher IL-5R alpha expression than those who were homozygous for the G allele.
  
  
  CONCLUSIONS
  The genetic association between CCR3 polymorphisms and the number of circulating eosinophils was revealed as a novel finding. These associations were more pronounced when the CCR3 polymorphisms were paired with polymorphisms in IL5RA. The protein expression levels of CCR3 and IL-5R alpha on peripheral blood eosinophils are associated with the polymorphisms on their own genes.
  
  
  CONCLUSIONS
  The identification of single nucleotide polymorphisms and haplotypes of CCR3 and IL5RA might be useful in developing markers for intermediate phenotypes of eosinophil number and in designing strategies to control diseases related to hypereosinophilia.
authors.affiliation: Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Bucheon Hospital, Gyeonggi Do, Korea.
authors.forename: June-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Chang
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Se-Min
authors.initials: SM
authors.lastname: Park
authors.forename: Yong Mok
authors.initials: YM
authors.lastname: Lee
authors.forename: Soo Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Taiyoun
authors.initials: T
authors.lastname: Rhim
authors.forename: Il Yup
authors.initials: IY
authors.lastname: Chung
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D002648:Child; D004802:Eosinophilia / Q000235:genetics*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D053666:Interleukin-5 Receptor alpha Subunit / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054397:Receptors, CCR3 / Q000235:genetics*
chemical_list: C515350:CCR3 protein, human; D053666:Interleukin-5 Receptor alpha Subunit; D054397:Receptors, CCR3