Association of Eotaxin gene family with asthma and serum total IgE

Abstract

The Eotaxin gene family (Eotaxin1, Eotaxin2 and Eotaxin3) recruits and activates CCR3-bearing cells such as eosinophils, mast cells and Th2 lymphocytes that play a major role in allergic disorders. To date, the effect of polymorphisms of Eotaxin genes on asthma phenotypes has not been thoroughly examined. In our research, we sequenced whole regions of the Eotaxin gene family to identify polymorphisms, which may be involved in the development of asthma and total serum IgE. We have identified 37 SNPs in the Exotaxin gene family (Exotaxin1, 2 and 3), and 17 common polymorphic sites were selected for genotyping in our asthma cohort (n=721). Statistical analysis revealed that the EOT2+1265A>G G* allele showed significantly lower frequency in asthmatics than in normal healthy controls (0.14 versus 0.23, P=0.002), and that distribution of the EOT2+1265A>G G* allele-containing genotypes was also much lower in asthmatics (26.3 versus 40.8%, P=0.003). In addition, a non-synonymous SNP in Eotaxin1, EOT1+123Ala>Thr showed significant association with total serum IgE levels (P=0.002-0.02). The effect of EOT1+123Ala>Thr on total serum IgE appeared in a gene-dose-dependent manner. Our findings suggest that the development of asthma may be associated with EOT2+1265A>G polymorphisms, and the susceptibility to high IgE production may be attributed to the EOT1+123Ala>Thr polymorphism. Eotaxin variation/haplotype information identified in this study might provide valuable insights into strategies for the control of asthma.

Association of eotaxin-2 gene polymorphisms with plasma eotaxin-2 concentration

“…Association of SNPs and haplotypes of eotaxin-2 gene with the plasma eotaxin-2 level Of the 16 SNPs identified in our previous study (Shin et al 2003), five SNPs were selected for larger-scale genotyping based on linkage disequilibriums (LDs) among SNPs and frequencies. Four polymorphisms (+734G fi A, +824C fi A, +1102T fi G, and +1193 fi A) showing low frequencies (<0.10) were excluded for further analysis.…”

“…Genotyping by single-base extension (SBE) and electrophoresis Primer extension reactions were performed with a SNaPshot ddNTP Primer Extension Kit (Applied Biosystems, Foster City, CA, USA), as described (Shin et al 2003). The DNA samples containing extension products and GeneScan 120-Liz-size standard solutions were added to Hi-Di formamide (Applied Biosystems).…”

“…Local eotaxin-2 promotes eosinophil accumulation into the airway, IL-13 production, and airway hyperreactivity in cooperation with IL-5 (Yang et al 2003) and recruits newly produced and CD34 + eosinophils after allergen exposure in animal study (Radinger et al 2004). We previously identified 16 novel single nucleotide polymorphisms (SNPs) of the eotaxin-2 gene and demonstrated a significant association between one SNP in eotaxin-2 (CCL24+1272 A fi G G* allele) and a lower risk of asthma (Shin et al 2003). The known biological effects of eotaxin-2 (Ying et al 1999;Rojas-Ramos et al 2003;Yang et al 2003;Radinger et al 2004) and the protective effect of the CCL24+1272 A fi G G* allele (Shin et al 2003) prompted us to compare the plasma eotaxin-2 levels in asthmatics and normal controls to validate functional evidence for the association between the genetic polymorphism of the eotaxin-2 gene and asthma.…”

“…We previously identified 16 novel single nucleotide polymorphisms (SNPs) of the eotaxin-2 gene and demonstrated a significant association between one SNP in eotaxin-2 (CCL24+1272 A fi G G* allele) and a lower risk of asthma (Shin et al 2003). The known biological effects of eotaxin-2 (Ying et al 1999;Rojas-Ramos et al 2003;Yang et al 2003;Radinger et al 2004) and the protective effect of the CCL24+1272 A fi G G* allele (Shin et al 2003) prompted us to compare the plasma eotaxin-2 levels in asthmatics and normal controls to validate functional evidence for the association between the genetic polymorphism of the eotaxin-2 gene and asthma. Here, we evaluated whether the plasma eotaxin-2 level is dependent on the polymorphism of the eotaxin-2 gene.…”

The association of eotaxin-2 and eotaxin-3 gene polymorphisms in a Korean population with ulcerative colitis

“…Recently, the single nucleotide polymorphisms (SNPs) in the eotaxin gene family were identified (Shin et al, 2003;. We previously reported that the Eo2 +179T C, Eo2 +275C T of eotaxin-2 and the Eo3 +2497T G of eotaxin-3 are significantly associated with susceptibility to asthma, and also demonstrated that the Eo3 +2497T G is related to serum total IgE level, and to the peripheral blood eosinophil counts in asthma patients .…”