title: Polymorphisms of the Bcl-2 family member bfl-1 in children with atopic dermatitis.
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.
authors.affiliation: School of Biological Sciences, University of Manchester, Manchester, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gray
authors.forename: Helen
authors.initials: H
authors.lastname: Stewart
authors.forename: Vera
authors.initials: V
authors.lastname: Pravica
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fryer
authors.forename: Warren
authors.initials: W
authors.lastname: Lenney
authors.forename: Ian V
authors.initials: IV
authors.lastname: Hutchinson
authors.forename: Peter D
authors.initials: PD
authors.lastname: Arkwright
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003876:Dermatitis, Atopic / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
chemical_list: C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2