Genome-wide association study identifies CDH13 as a susceptibility gene for rhododendrol-induced leukoderma.
Pigment Cell Melanoma Res
; 33(6): 826-833, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32558222
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.
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MEDLINE
Assunto principal:
Vitiligo
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Caderinas
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Predisposição Genética para Doença
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Estudo de Associação Genômica Ampla
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article