Association of TNFA gene polymorphism at position-308 with susceptibility to irritant contact dermatitis

Mechanisms underlying susceptibility to skin irritants are not clearly unde rstood. Cytokines play a key role in inflammation, and functional polymorph isms in cytokine genes may affect responses to irritants. We investigated t he relationship between polymorphism in the tumor necrosis factor (TNF) alp ha-chain gene and responses to irritants. Volunteers (n=221) tested with so dium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided int o 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 i ncrease 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 g enotype P=0.048). In the BKC low irritant-threshold group, we found a signi ficant increase in the A allele (P=0.002) and AA genotype (P=0.016). Indivi duals with a low threshold to both irritants demonstrated a significant inc rease (P=0.002) in the A allele. This is the first description of a nonatop ic genetic marker for irritant susceptibility in normal individuals. Genoty ping for the TNF-308 polymorphism may thus contribute to screening of indiv iduals deemed at risk of developing irritant contact dermatitis.