Association between TNFA-308 G/A polymorphism and sensitization to para-phenylenediamine: a case-control study

Para-phenylenediamine (PPD) and related chemicals are common contact sensitizers, frequently causing allergic contact dermatitis (ACD). The cytokine tumor necrosis factor-alpha (TNF-alpha) plays a key role in contact sensitization. In this case-control study, we evaluated the distribution of variations in the regulatory region of the gene for TNF-alpha (TNFA-308 G/A) in 181 Caucasian individuals with a history of ACD and sensitization to PPD and 161 individuals with no history of sensitization to PPD. The frequency of GA or AA TNFA genotypes was significantly higher in individuals sensitized to PPD than in age- and gender-matched controls giving an odds ratio (OR) of 2.16 (95% confidence interval, CI: 1.35-3.47; P = 0.0016). This relation was even more pronounced when restricting cases to females over 45 years (OR = 3.71; 95% CI: 1.65-8.31; P = 0.0017) vs younger females (less than or equal to 45 years; OR = 2.41; 95% CI: 1.03-5.65; P = 0.044) or males (OR = 1.05; 95% CI: 0.449-2.47; P = 1.0). In addition, a logistic regression model revealed a significant effect for TNFA-308 AA and AG vs GG genotype (point estimate = 2.152; 95% Wald CI: 1.332-3.477). These findings suggest a possible role for the TNFA-308 genetic polymorphism as a susceptibility factor for chemically induced ACD.