Association analysis of CD40 polymorphisms with asthma and the level of serum total IgE.

Abstract:

RATIONALE:The CD40 protein plays important roles in cell-mediated and humoral immune responses, especially in immunoglobulin class-switching to IgE. OBJECTIVES: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. MEASUREMENTS AND 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

Park JH,Chang HS,Park CS,Jang AS,Park BL,Rhim TY,Uh ST,Kim YH,Chung IY,Shin HD

doi

10.1164/rccm.200609-1286OC

subject

Has Abstract

pub_date

2007-04-15 00:00:00

pages

775-82

issue

8

eissn

1073-449X

issn

1535-4970

pii

200609-1286OC

journal_volume

175

pub_type

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