title: Association analysis of CD40 polymorphisms with asthma and the level of serum total IgE.
abstract: BACKGROUND
  The CD40 protein plays important roles in cell-mediated and humoral immune responses, especially in immunoglobulin class-switching to IgE.
  
  
  OBJECTIVE
  We tested the association of CD40 polymorphisms with the risk of asthma and the level of serum IgE and investigated the functional effect of associated polymorphisms on the expression of CD40.
  
  
  METHODS
  We identified 17 CD40 single-nucleotide polymorphisms (SNPs) in the Korean population by direct sequencing, and we genotyped 7 of these in 487 subjects with asthma and in 161 normal subjects. Cell-surface expression of CD40 for B-cell lines of various SNP genotypes was measured using flow cytometry. The effects of SNPs in the promoter and 5'-untranslated regions (UTRs) of CD40 were assessed using pGL3 luciferase and enhanced green fluorescent protein (EGFP) reporter systems, respectively.
  
  
  RESULTS
  None of the SNPs was associated with asthma risk, but total serum IgE levels were associated with the -580G>A and -1C>T polymorphisms in subjects with asthma (p = 0.007 and 0.005, respectively). The total amount of IgE was highest in the -580A or -1C homozygotes. More CD40 was expressed in B cells with the -1C allele than in those with the -1T allele (p < 0.001). EGFP expression from the CD40 5'-UTR-EGFP construct was higher for the -1C allele than the -1T allele. The -580G>A SNP did not affect promoter activity, even after IFN-gamma stimulation.
  
  
  CONCLUSIONS
  CD40 gene polymorphisms exert a genetic effect on IgE production in patients with asthma through translational regulation of CD40 expression on B cells.
authors.affiliation: Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Hospital, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, Republic of Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Chang
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: An-Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Tai Youn
authors.initials: TY
authors.lastname: Rhim
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Il Yup
authors.initials: IY
authors.lastname: Chung
authors.forename: Hyung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000097:blood* / Q000235:genetics*; D019013:CD40 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007723:Korea; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment
chemical_list: D019013:CD40 Antigens; D007073:Immunoglobulin E