title: Association of TNFA gene polymorphism at position -308 with susceptibility to irritant contact dermatitis.
abstract: Mechanisms underlying susceptibility to skin irritants are not clearly understood. Cytokines play a key role in inflammation, and functional polymorphisms in cytokine genes may affect responses to irritants. We investigated the relationship between polymorphism in the tumor necrosis factor (TNF) alpha-chain gene and responses to irritants. Volunteers (n=221) tested with sodium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided into responders and nonresponders and high and low irritant-threshold groups. DNA was assayed for the TNF-308 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism method. There was a significant increase in the A allele (P=0.030) and AA genotype (P=0.023) in both the SDS low irritant-threshold group and in SDS responders (A allele P=0.022, AA genotype P=0.048). In the BKC low irritant-threshold group, we found a significant increase in the A allele (P=0.002) and AA genotype (P=0.016). Individuals with a low threshold to both irritants demonstrated a significant increase (P=0.002) in the A allele. This is the first description of a nonatopic genetic marker for irritant susceptibility in normal individuals. Genotyping for the TNF-308 polymorphism may thus contribute to screening of individuals deemed at risk of developing irritant contact dermatitis.
authors.affiliation: St. John's Institute of Dermatology, St. Thomas's Hospital, London, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Allen
authors.forename: S H
authors.initials: SH
authors.lastname: Wakelin
authors.forename: D
authors.initials: D
authors.lastname: Holloway
authors.forename: S
authors.initials: S
authors.lastname: Lisby
authors.forename: O
authors.initials: O
authors.lastname: Baadsgaard
authors.forename: J N
authors.initials: JN
authors.lastname: Barker
authors.forename: J P
authors.initials: JP
authors.lastname: McFadden
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001548:Benzalkonium Compounds / Q000009:adverse effects; D017453:Dermatitis, Irritant / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007509:Irritants / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010328:Patch Tests; D011110:Polymorphism, Genetic; D012967:Sodium Dodecyl Sulfate / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D001548:Benzalkonium Compounds; D007509:Irritants; D014409:Tumor Necrosis Factor-alpha; D012967:Sodium Dodecyl Sulfate