High-level expression of early growth response-1 and association of polymorphism with total IgE and atopy in allergic rhinitis adults.

BACKGROUND: Early growth response-1 (Egr-1) is expressed in human airways and its polymorphisms have been associated with total IgE and atopy in asthmatic patients. We investigated the effects of Chinese-tagging single nucleotide polymorphism (SNP) of Egr-1 and its mRNA expression on allergic rhinitis (AR) traits. METHODS: Among 214 Chinese AR adults and 259 controls, tag SNP -4071 A-->G was genotyped and mRNA expression in peripheral blood was quantified by real-time PCR. RESULTS: Egr-1 mRNA expression was significantly higher in patients than controls (median of 0.23 vs 0.15 fold GAPDH expression; p<0.001). Its expression was not associated with -4071 polymorphism. However, significant correlations were found between -4071 A-->G with increased plasma total IgE (p=0.028) and atopy (p=0.030) in patients. Logistic regression confirmed the association (p=0.034) with age and gender adjusted. Patients homozygous for the A allele had a 2.3-fold and 1.9-fold risks, respectively of having increased plasma total IgE and atopy than those G allele carriers. CONCLUSIONS: We showed high levels of Egr-1 mRNA expression and demonstrated a significant association of polymorphism with increased plasma total IgE and atopy in AR patients. It may be useful to explore the pharmacogenetics of Egr-1 inhibitors.

Association of plasma soluble CTLA-4 with lung function and gene polymorphism in Chinese asthmatic children.

BACKGROUND: Cytotoxic T lymphocyte antigen 4 (CTLA-4) is known to downregulate the T(H)2 immune response. Recent studies have suggested an association of CTLA-4 polymorphisms with allergic diseases. We investigated the effects of single nucleotide polymorphisms (SNPs) of CTLA-4 on asthma traits and plasma sCTLA-4 in 298 Chinese asthmatic children and 175 controls. METHODS: Plasma sCTLA-4, total and allergen-specific IgE concentrations were measured by enzyme immunoassay. Six SNPs, namely -1147CT, +49AG, CT60, JO31, JO30 and JO27_1, in CTLA-4 were genotyped by restriction fragment length polymorphism. RESULTS: Plasma sCTLA-4 was negatively associated with FEV(1)/FVC (r = -0.146, p = 0.036) among our asthmatic patients. Analysis of locus-locus interaction by generalized multifactor dimensionality reduction showed that -1147CT was the best model for plasma sCTLA-4 with a cross-validation consistency of 10 out of 10 and a prediction error of 40.9% (p < 0.001). Multivariate regression analysis confirmed the association between plasma sCTLA-4 concentration with -1147CT among the 6 SNPs tested (p = 0.002) after adjustment for gender and age. The plasma sCTLA-4 concentration was significantly lower in patients homozygous for the C allele than in T allele carriers (p = 0.001). There was also a significant association between the most common haplotypes with low sCTLA-4 in asthmatics. We could not find any significant association between plasma total IgE, atopy and lung function with the 6 SNPs after Bonferroni correction. CONCLUSIONS: Plasma sCTLA-4 is associated with lung function and -1147CT polymorphism in Chinese asthmatic children. This may help to identify CTLA-4 signaling as a potential therapeutic target in asthma.

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.