論文

査読有り 国際誌
2020年6月18日

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

Pigment cell & melanoma research
  • 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 Hayashi
  • ,
  • Yutaka Hozumi
  • ,
  • Tamio Suzuki

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/pcmr.12904

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.

リンク情報
DOI
https://doi.org/10.1111/pcmr.12904
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32558222

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