The role of Glutathione S-Transferase (GST) and Claudin-1 (CLDN1) gene polymorphisms in contact sensitization: a cross-sectional study

Background:  While contact sensitization is frequent in the general population and arises from excessive or repeated skin exposure to chemicals and metals, little is known about genetic susceptibility. Objectives:  To determine the role of glutathione s-transferases (GST) and claudin-1 (CLDN1) gene polymorphisms on the risk of contact sensitization taking common filaggrin gene (FLG) mutations into account. Methods:  A total of 3471 adult Danes from the general population were standard patch tested and filled out a questionnaire on general health. They were genotyped for the following polymorphisms: GSTM1 and T1 deletion, GSTP1 SNP rs1695, four CLDN1 SNPs (rs893051, rs9290927, rs9290929 and rs17501010), and FLG null (R501X and 2282del4) Results:  In individuals without ear piercings, a higher prevalence of nickel sensitization was found in those with the minor allele of CLDN1 SNP rs9290927 (p(trend) =0.013). For CLDN1 rs17501010, contact sensitization to organic compounds was associated with the major allele (p(trend) =0.031). The risk pattern was also identified for self-reported nickel dermatitis (p(trend) =0.011). The fragrance sensitization prevalence differed in a pair-wise comparison of the CLDN1 rs893051 SNP genotypes (p=0.022) with the minor allele being associated with a higher prevalence. The associations were confirmed in logistic regression analyses. Conclusions:  The CLDN1 polymorphisms rs9290927, rs893051, and rs17501010 were associated with nickel contact sensitization in individuals without ear piercings, contact sensitization to fragrances, and with both organic compounds and nickel contact dermatitis, respectively. We could not find associations between GST polymorphisms and contact sensitization. FLG mutations did not affect the observed associations.