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The G\/G and G\/A genotypes correspond to the wet type of earwax, whereas A\/A corresponds to the dry type. Wide ethnic differences exist in the frequencies of those alleles, reflecting global migratory waves of the ancestors of humankind. We herein provide the evidence that this genetic polymorphism has an effect on the Alinked glycosylation of ABCC11, intracellular sorting, and proteasomal degradation of the variant protein. Immunohistochemical studies with cerumen gland\u2010containing tissue specimens revealed that the ABCC11 WT protein was localized in intracellular granules and large vacuoles, as well as at the luminal membrane of secretory cells in the cerumen gland, whereas granular or vacuolar localization was not detected for the SNP (Arg180) variant. This SNP variant lacking A\u2010linked glycosylation is recognized as a misfolded protein in the endoplasmic reticulum and readily undergoes ubiquitina\u2010tion and proteasomal degradation, which determines the dry type of earwax as a mendelian trait with a recessive phenotype. For rapid genetic diagnosis of axillary osmidrosis and potential risk of breast cancer, we developed specific primers for the SmartAmp method that enabled us to clinically genotype the\n                    <jats:italic>ABCC11<\/jats:italic>\n                    gene within 30 min.\u2014Toyoda, Y.,Sakurai, A., Mitani, Y., Nakashima, M., Yoshiura, K., Nakagawa, H., Sakai, Y., Ota, I., Lezhava, A., Hayashizaki, Y., Niikawa, N., Ishikawa, T. Earwax, osmidrosis, and breast cancer: why does one SNP (538G&gt; A) in the human ABC transporter ABCC11 gene determine earwax type?\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 2001\u20132013 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.09-129098","type":"journal-article","created":{"date-parts":[[2009,4,21]],"date-time":"2009-04-21T22:39:19Z","timestamp":1240353559000},"page":"2001-2013","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Earwax, osmidrosis, and breast cancer: why does one SNP (538G&gt;A) in the human ABC transporter\n                    <i>ABCC11<\/i>\n                    gene determine earwax type?"],"prefix":"10.1096","volume":"23","author":[{"given":"Yu","family":"Toyoda","sequence":"first","affiliation":[{"name":"Department of Biomolecular Engineering Graduate School of Bioscience and Biotechnology Tokyo Institute of Technology Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering Graduate School of Bioscience and Biotechnology Tokyo Institute of Technology Yokohama Japan"},{"name":"Omics Science Center (OSC) RIKEN Yokohama Institute Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Mitani","sequence":"additional","affiliation":[{"name":"Omics Science Center (OSC) RIKEN Yokohama Institute Yokohama Japan"},{"name":"Tissue and Histopathology Section Atomic Bomb Disease Institute Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koh-ichiro","family":"Yoshiura","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering Graduate School of Bioscience and Biotechnology Tokyo Institute of Technology Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Fujita Health University Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Ota","sequence":"additional","affiliation":[{"name":"Omics Science Center (OSC) RIKEN Yokohama Institute Yokohama Japan"},{"name":"Department of Gastroenterological Surgery Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Lezhava","sequence":"additional","affiliation":[{"name":"Omics Science Center (OSC) RIKEN Yokohama Institute Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihide","family":"Hayashizaki","sequence":"additional","affiliation":[{"name":"Omics Science Center (OSC) RIKEN Yokohama Institute Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Niikawa","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan"},{"name":"Research Institute of Personalized Health Sciences Health Sciences University of Hokkaido Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Engineering Graduate School of Bioscience and Biotechnology Tokyo Institute of Technology Yokohama Japan"},{"name":"Omics Science Center (OSC) RIKEN Yokohama Institute Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2005.12.046"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-007-0356-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajpa.1330620115"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.173.3994.347"},{"key":"e_1_2_7_6_1","first-page":"597","article-title":"Apocrine secretory mechanism: recent findings and unresolved problems","volume":"18","author":"Gesase A.P.","year":"2003","journal-title":"Histol. 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