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

Area of Science:

• Genetics
• Dermatology
• Toxicology

Background:

• Topical skin-lightening agents, like rhododendrol (RD), can cause unexpected side effects such as RD-induced leukoderma (RIL).
• The genetic underpinnings of chemical-induced vitiligo, including RIL, remain largely unexplored on a genome-wide scale.

Purpose of the Study:

• To conduct the first genome-wide association study (GWAS) to identify genetic susceptibility factors for RD-induced leukoderma (RIL).
• To investigate the role of identified genes in the pathogenesis of chemical-induced vitiligo.

Main Methods:

• A genome-wide association study (GWAS) was performed on 147 RIL cases and 112 controls.
• T-cadherin (T-cad) knockdown was utilized in cultured human melanocytes to assess its functional role.
• Gene expression analysis was conducted to examine pathways related to RD sensitivity.

Main Results:

• CDH13, encoding T-cadherin (T-cad), emerged as the strongest susceptibility gene for RIL.
• T-cad knockdown significantly increased sensitivity to RD in human melanocytes.
• Evidence suggests T-cad influences RD sensitivity through tyrosinase regulation or apoptotic pathways.

Conclusions:

• T-cadherin (CDH13) is a significant genetic susceptibility factor for RD-induced leukoderma.
• T-cad may play a role in other forms of chemical-induced vitiligo, such as that caused by monobenzyl ether of hydroquinone.
• This GWAS provides a valuable model for understanding the genetic basis of chemical-induced vitiligo.