Genome-wide association study identifies CDH13 as a susceptibility gene for rhododendrol-induced leukoderma

Ken Okamura, Yuko Abe, Izumi Naka, Jun Ohashi, Akiko Yagami, Kayoko Matsunaga, Yui Kobayashi, Kazuyoshi Fukai, Atsushi Tanemura, Ichiro Katayama, Yukiko Masui, Akiko Ito, Toshiharu Yamashita, Hiroshi Nagai, Chikako Nishigori, Naoki Oiso, Yumi Aoyama, Yuta Araki, Toru Saito, Masahiro HayashiYutaka Hozumi, Tamio Suzuki

Research output: Contribution to journalArticlepeer-review

Abstract

Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol; trade name: Rhododenol [RD]), which is used in topical skin-lightening cosmetics, was unexpectedly reported in Japan to induce leukoderma or vitiligo called RD-induced leukoderma (RIL) after repeated application. To our knowledge, no studies have investigated chemical-induced vitiligo pathogenesis on a genome-wide scale. Here, we conducted a genome-wide association study (GWAS) for 147 cases and 112 controls. CDH13, encoding a glycosylphosphatidylinositol-anchored protein called T-cadherin (T-cad), was identified as the strongest RIL susceptibility gene. RD sensitivity was remarkably increased by T-cad knockdown in cultured normal human melanocytes. Furthermore, we confirmed tyrosinase upregulation and downregulation of the anti-apoptotic molecules (BCL-2 and BCL-XL), suggesting that T-cad is associated with RD via tyrosinase or apoptotic pathway regulation. Finally, monobenzyl ether of hydroquinone sensitivity also tended to increase with T-cad knockdown, suggesting that the T-cad could be a candidate susceptibility gene for RIL and other chemical-induced vitiligo forms. This is the first GWAS for chemical-induced vitiligo, and it could be a useful model for studying the disease's genetic aspects.

Original languageEnglish
Pages (from-to)826-833
Number of pages8
JournalPigment Cell and Melanoma Research
Volume33
Issue number6
DOIs
Publication statusPublished - 01-11-2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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