Polymorphisms of the Bcl-2 family member bfl-1 in children with atopic dermatitis

Authors


P. D. Arkwright, Booth Hall Children's Hospital, Charlestown Rd., Manchester, M9 7AA, United Kingdom
Tel.: + 44 161 918 5535
Fax: + 44 161 918 5143
E-mail: peter_arkwright@lineone.net

Abstract

T lymphocytes accumulating in the skin of patients with atopic dermatitis (AD) have a prolonged survival and are key mediators of this inflammatory disease. The anti-apoptotic bfl-1 gene is unique in that it is the only member of the Bcl-2 family that is transcriptionally regulated by inflammatory cytokines and might therefore be important in promoting the survival of effector T cells in patients with AD. The aim of this study was to determine whether polymorphisms in the bfl-1 gene are associated with a predisposition to childhood AD. Four bfl-1 gene, single nucleotide polymorphisms (SNPs) were studied by ARMS-PCR in 105 Caucasian children with moderately severe AD and 110 non-atopic adult controls. In addition to the known polymorphisms of exon 1 (+141*A/G, +202*G/T, +303*A/G), we described a novel polymorphism in the promoter region of the gene (−1182*G/C). We found a significant difference in bfl-1 +141 genotype [OR (95% CI) 5.1 (1.0–25.2)], as well as bfl-1−1182:+141:+202:+303 G:A:G:A/G:A:G:A diplotype frequencies [3.5 (1.0–12.2)] in AD (p < 0.05). The study thus provides evidence for an association between bfl-1 polymorphisms and the genetic predisposition to AD.

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