Genetic factors in contact allergy--review and future goals

The genetics of contact allergy are still only partly understood, despite decades of research; this might be a consequence of inadequately defined phenotypes used in the past. A recommendation is to study an extreme phenotype, namely, polysensitization (sensitization to three or more unrelated allergens). Another approach to unravel the genetics of contact allergy is the study of candidate genes. In this review, we summarize studies on the associations between genetic variation (e.g. single-nucleotide polymorphisms) in certain candidate genes and contact allergy. Polymorphisms and mutations affecting the following proteins were studied: (i) filaggrin; (ii) N-acetyltransferase (NAT) 1 and 2; (iii) glutathione-S-transferase (GST) M and T; (iv) manganese superoxide dismutase; (v) angiotensin-converting enzyme (ACE); (vi) tumour necrosis factor (TNF); and (vii) interleukin-16 (IL-16). The polymorphisms of NAT1, NAT2, GSTM, GSTT, ACE, TNF and IL-16 were shown to be associated with an increased risk of contact allergy. In one of our studies, the increased risk conferred by the TNF and IL-16 polymorphisms was confined to polysensitized individuals. Other relevant candidate genes may be identified by studying diseases related to contact allergy in terms of clinical symptoms, a more general pathology (inflammation), and possibly an overlapping genetic background, such as irritant contact dermatitis.