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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\u2014p.Gln126Ter (rs72552713) and p.Gln141Lys (rs2231142)\u2014reportedly 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 (<jats:italic>P<\/jats:italic>\u2009=\u20090.012). 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 <jats:italic>ABCG2<\/jats:italic> genotypes in the non-CAD group was significantly lower than in the general Japanese population (<jats:italic>P<\/jats:italic>\u2009=\u20090.045). 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 \u201cphotosensitivity of unknown cause.\u201d<\/jats:p>","DOI":"10.1007\/s13577-021-00534-y","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T08:02:49Z","timestamp":1621411369000},"page":"1082-1086","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Porphyrin accumulation in humans with common dysfunctional variants of ABCG2, a porphyrin transporter: potential association with acquired photosensitivity"],"prefix":"10.1007","volume":"34","author":[{"given":"Masayuki","family":"Sakiyama","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4302-8719","authenticated-orcid":false,"given":"Hirotaka","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7411-0531","authenticated-orcid":false,"given":"Yu","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuiko","family":"Yonekura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6654-0726","authenticated-orcid":false,"given":"Akiyoshi","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihide","family":"Higashino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5021-1613","authenticated-orcid":false,"given":"Yusuke","family":"Kawamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihiro","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1497-487X","authenticated-orcid":false,"given":"Nariyoshi","family":"Shinomiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2244-6332","authenticated-orcid":false,"given":"Takahiro","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"534_CR1","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.clindermatol.2016.05.006","volume":"34","author":"AF Monteiro","year":"2016","unstructured":"Monteiro AF, Rato M, Martins C. Drug-induced photosensitivity: photoallergic and phototoxic reactions. Clin Dermatol. 2016;34:571\u201381.","journal-title":"Clin Dermatol"},{"key":"534_CR2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.2165\/00128071-200203040-00002","volume":"3","author":"TP Millard","year":"2002","unstructured":"Millard TP, Hawk JL. Photosensitivity disorders: cause, effect and management. Am J Clin Dermatol. 2002;3:239\u201346.","journal-title":"Am J Clin Dermatol"},{"key":"534_CR3","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1001\/archderm.1994.01690100068011","volume":"130","author":"HW Lim","year":"1994","unstructured":"Lim HW, Morison WL, Kamide R, Buchness MR, Harris R, Soter NA. Chronic actinic dermatitis. An analysis of 51 patients evaluated in the United States and Japan. 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The other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Ethics Committee of the National Defense Medical College (No. 2364; approved on 2015\/10\/27).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}