Association analysis of CD40 polymorphisms with asthma and the level of serum total IgE.
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.
Park
Ju Hyun
JH
Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Hospital, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, Republic of Korea.
Chang
Hun Soo
HS
Park
Choon-Sik
CS
Jang
An-Soo
AS
Park
Byung Lae
BL
Rhim
Tai Youn
TY
Uh
Soo-Taek
ST
Kim
Yong Hoon
YH
Chung
Il Yup
IY
Shin
Hyung Doo
HD
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
D019013:CD40 Antigens; D007073:Immunoglobulin E