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Association between a common IL10 distal promoter haplotype and IgE production in individuals with atopic dermatitis
Author(s) -
Lacy K.,
Archer C.,
Wood N.,
Bidwell J.
Publication year - 2009
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.2009.00857.x
Subject(s) - haplotype , single nucleotide polymorphism , locus (genetics) , genetics , biology , snp , atopic dermatitis , promoter , genotype , immunology , gene , gene expression
Summary Atopic dermatitis (AD) is a genetically determined inflammatory skin disease characterized by abnormal cytokine production, including increased production of interleukin 10 ( IL10 ). Single nucleotide polymorphisms (SNP) and haplotypes in the IL10 gene promoter region on chromosome 1q31‐32 have been implicated in several inflammatory diseases, but generally, only SNPs proximal to the transcription start site (TSS) have been investigated. The aim of this study was to identify proximal, distal and combined haplotype sets in the IL10 promoter region and to study their association with clinical phenotypes in atopic dermatitis. SNPs at positions –3575, –2849, –2779, –2763, –1082, –851, –819 and –592 in the IL10 promoter region were genotyped in individuals with atopic dermatitis ( n = 47) and nonatopic control subjects ( n = 40) using polymerase chain reaction‐based techniques and induced heteroduplex generator (IHG) analysis. Pan‐promoter, TSS‐proximal and TSS‐distal haplotypes were reconstructed using phase analysis. Fifteen haplotypes representing all eight SNPs were identified. Subgrouping identified four 4‐locus and three 3‐locus TSS‐proximal haplotypes; and nine 4‐locus TSS‐distal haplotypes. No difference was found in haplotype or SNP frequencies between the AD and control groups, or between patients with mild or severe disease. However, a common 4‐locus TSS‐distal haplotype (TGAC) was significantly increased in patients with IgE levels over 1000 kIU L −1 . This study is the first to analyse the association between haplotype groups in the IL10 promoter region and clinical phenotypes in AD. We have demonstrated a significant association between the TSS‐distal haplotype TGAC, and IgE levels in AD patients. It remains to be shown if there is an association between the TGAC haplotype and IL10 production, which might account for the stimulation of IgE production.