Photosensitivity is a skin reaction disorder mediated by phototoxic and/or photoallergic mechanisms. The accumulation of
porphyrins is generally considered to induce
phototoxicity.
ATP-binding cassette subfamily G member 2 (ABCG2) has been identified as a transporter of
porphyrins and its common variants-p.Gln126Ter (rs72552713) and p.Gln141Lys (rs2231142)-reportedly decrease the function of
porphyrin transport in vitro; however, the physiological importance of ABCG2 as a
porphyrin transporter remains to be fully elucidated. We herein investigated whether ABCG2 dysfunction could lead to
porphyrin accumulation and photosensitivity in Japanese subjects, and found it to be significantly correlated with erythrocyte
protoporphyrin levels (P = 0.012). This appears to be the first clinical finding of ABCG2 dysfunction-associated
protoporphyrin accumulation in humans. We divided the patients into a chronic actinic
dermatosis (CAD) group and a non-CAD group. CAD was diagnosed based on the criteria of reduced minimal
erythema doses to ultraviolet B (UVB) and/or ultraviolet A (UVA). The non-CAD group was composed of patients who exhibited normal reactions to UVB and UVA on phototesting, but had histories of recurrent
erythema/papules on sun-exposed areas. Estimated ABCG2 function according to ABCG2 genotypes in the non-CAD group was significantly lower than in the general Japanese population (P = 0.045). In contrast, no difference was found in ABCG2 function between the CAD group and the general population, suggesting that ABCG2 dysfunction might be a genetic factor in non-CAD patients with clinical photosensitivity. In this context, genetic dysfunction of ABCG2 might be an overlooked pathological etiology of "photosensitivity of unknown cause."