Recent progress in the genetics of generalized vitiligo

J Genet Genomics. 2011 Jul 20;38(7):271-8. doi: 10.1016/j.jgg.2011.05.005. Epub 2011 Jun 12.


Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo (GV), the predominant form of the disorder, results from autoimmune loss of melanocytes from affected regions. GV is a "complex trait", inherited in a non-Mendelian polygenic, multifactorial manner. GV is epidemiologically associated with other autoimmune diseases, both in GV patients and in their close relatives, suggesting that shared genes underlie susceptibility to this group of diseases. Early candidate gene association studies yielded a few successes, such as PTPN22, but most such reports now appear to be false-positives. Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies (GWAS) of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes. Together, these genes highlight biological systems and pathways that reach from the immune cells to the melanocyte, and provide insights into both disease pathogenesis and potential new targets for both treatment and even prevention of GV and other autoimmune diseases in genetically susceptible individuals.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Autoimmune Diseases / genetics*
  • DNA-Binding Proteins / genetics*
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Melanocytes / immunology*
  • Melanocytes / metabolism
  • Metabolic Networks and Pathways / genetics
  • Multifactorial Inheritance / genetics
  • NLR Proteins
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Regulatory Factor X Transcription Factors
  • Transcription Factors / genetics*
  • Vitiligo / genetics*
  • X-Box Binding Protein 1


  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • NLR Proteins
  • NLRP1 protein, human
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22