Porphyrin accumulation in humans with common dysfunctional variants of ABCG2 , a porphyrin transporter: potential association with acquired photosensitivity

AbstractPhotosensitivity 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 porphyr in 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 toABCG2 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...
Source: Human Cell - Category: Cytology Source Type: research