Association of early growth response-1 gene polymorphisms with total IgE and atopy in asthmatic children

Authors


Christopher W. K. Lam, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Tel: +852 2632 2332
Fax: +852 2636 5090
E-mail: waikeilam@cuhk.edu.hk

Abstract

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 β 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, IgElog 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.

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