A Single Nucleotide Polymorphism on the Promoter of eotaxin1 Associates with Its mRNA Expression and Asthma Phenotypes

Abstract

Eotaxin1 plays a pivotal role in eosinophil-associated inflammation. Previously, we demonstrated 14 single-nucleotide polymorphisms (SNPs) in the human eotaxin1 gene and the association between the EOT+67G>A allele and the level of IgE. In this study, we investigated the association between the SNPs and plasma eotaxin1 levels, peripheral blood eosinophil counts, and PC20 methacholine values in normal and asthmatic subjects, and the effects of SNPs on the process of eotaxin1 production. The EOT−576C>T and EOT−384A>G polymorphisms and haplotypes (ht1 and ht4) were significantly associated with plasma eotaxin1 levels in the asthmatics (p < 0.001–0.040). The log [plasma eotaxin1] values correlated with the log [serum total IgE] values in the asthmatics and the normal controls (p = 0.012 and p = 0.004, respectively), and with the log [PC20 methacholine] values in the asthmatics (p = 0.014). A DNA-protein complex was formed with EOT−384A>G, but not with the other SNPs of the promoter. The interaction was stronger with the minor allele than with the common allele, and was reduced upon TNF-α exposure. TNF-α-stimulated PBMCs from the asthmatics with the minor allele homozygote expressed significantly lower levels of eotaxin1 mRNA than those from individuals with the common allele. The EOT+67G>A polymorphism, which substitutes alanine with threonine, did not affect eotaxin1 production or activity. Our data suggest that the EOT−384A>G SNP participates in the regulation of eotaxin1 expression by providing a potential binding site for a repressor, and that the ANOVA of EOT-384A>G may predict asthma phenotypes.

Interleukin 3 and schizophrenia: the impact of sex and family history

“…Although it is not clear at this time whether variants of rs31400, rs31480 and rs2069803 change the expression of IL3, this scenario is likely, as demonstrated by promoter variants of other genes. 36,37 Despite all these information, we cannot exclude the possibility that these regulatory elements also regulate the expression of ACSL6 gene. Functional and expression studies are necessary to clarify this issue.…”

A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia

“…For instance, SNPs in the promoters of the TBX21 and eotaxin 1 genes and SNPs in the promoter and introns of the STAT4 gene have been shown to be associated with asthma (36)(37)(38). A SNP in the proximal promoter of the TCOF1 gene was found to be associated with and functionally relevant in Treacher Collins Syndrome, an autosomal-dominant craniofacial malformation (39).…”

Evaluation of a role of cytokine gene polymorphisms in development of bronchial asthma in the Republic of Bashkortostan

“…Частота гомозиготного по аллелю CCL11* 384G генотипа у больных БА (31,58 %) была также выше, чем в контроле (22 %), но различия не достигли уровня статистической зна чимости. По данным H.S.Chang et al, у гена, несу щего аллель CCL11* 384G полиморфного варианта 384A>G гена CCL11, способность связывать тран скрипционный фактор выше, чем у гена, имеющего аллель CCL11* 384A [12]. Ассоциация аллеля CCL11* 384G с БА ранее была выявлена у афроаме риканцев и индусов [13,14].…”