Association of early growth response-1 gene polymorphisms with total IgE and atopy in asthmatic children.
Early growth response-1 (Egr-1) is expressed in human airways and found to modulate tumor necrosis factor, immunoglobulin E (IgE), airway responsiveness, and interleukin-13-induced inflammation in mice. We investigated the effects of Chinese-tagging single nucleotide polymorphisms (SNPs) of Egr-1 on asthma traits in 298 Chinese asthmatic children and 175 controls, and a replication community cohort of 191 controls. Tag SNP (-4071 A-->G) and three additional SNPs (-1427 C-->T, -151 C-->T and IVS1 -42 C-->T) were genotyped by restriction fragment length polymorphism (RFLP). Significant associations were found between plasma total IgE concentration and -4071 A-->G (p = 0.008) and IVS1 -42 C-->T (p = 0.027) in asthmatic patients. After Bonferroni correction, only -4071 A-->G showed significant association. Multivariate regression analysis confirmed this significant association with a standardized coefficient beta of 0.156 (95% CI: 0.046-0.317; p = 0.009) in asthmatics among the three SNPs with age and gender-adjusted. In -4071 A-->G, IgE(log) was significantly higher in patients with the GG genotype than the AA genotype (p = 0.009). In addition, -4071 A-->G was significantly associated with atopy (p = 0.016) and high total IgE concentration (p = 0.030) among asthmatics. Patients with the G allele had a 3.5-fold risk of having atopy and a 2.0-fold risk of having high total IgE concentration than those homozygous for the A allele. This is the first report to show significant association of Egr-1 polymorphisms with plasma total IgE and atopy in asthmatics. It may help to explore the pharmacogenetics of Egr-1 inhibitors.
Chan
Iris H S
IH
Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong.
Tang
Nelson L S
NL
Leung
Ting F
TF
Huang
W
W
Lam
Yvonne Y O
YY
Wong
Gary W K
GW
Chan
Juliana C N
JC
Chan
Michael H M
MH
Wong
Chun K
CK
Zhang
Ya P
YP
Lam
Christopher W K
CW
D000293:Adolescent; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D002415:Cats / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003058:Cockroaches / Q000276:immunology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D004285:Dogs / Q000276:immunology; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000276:immunology; D000939:Epitopes; D005260:Female; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013147:Spirometry
D039741:Antigens, Dermatophagoides; D051766:Early Growth Response Protein 1; D000939:Epitopes; D007073:Immunoglobulin E