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The prevalence of vitiligo is reasonably consistent among different populations: ∼0.38% in Caucasians,1 0.34% in Afro-Caribbeans,2 0.46% in Indians,3 though perhaps somewhat less frequent in Han Chinese, 0.093%.4 Vitiligo appears to affect both genders equally, though women are overrepresented among patients seeking clinical care. Vitiligo can develop at any age,5 with a mean age-of-onset in Caucasian patients of about 24 years.6 The most common subtype, generalized vitiligo (GV), is an autoimmune disease that is associated with other autoimmune diseases in about 20%–30% of patients, most frequently autoimmune thyroid disease (Hashimoto's thyroiditis or Grave's disease), rheumatoid arthritis, psoriasis, type 1 diabetes (usually adult-onset), pernicious anemia, systemic lupus erythematosus, and Addison's disease.7
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Vitiligo is a multifactorial, polygenic disorder, with a complex pathogenesis that is not yet well understood.8 Of various theories of disease pathogenesis, the most accepted is that genetic and nongenetic factors interact to influence melanocyte function and survival, eventually leading to autoimmune destruction of melanocytes.7 Other suggested explanations have included defects of melanocyte adhesion,9 neurogenic damage,10 biochemical damage,11 autocytotoxicity,12 and others.
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Large-scale epidemiological surveys have shown that most cases of vitiligo occur sporadically, although about 15%–20% of patients have one or more affected first-degree relatives. Typically, familial aggregation of cases exhibits a non-Mendelian pattern suggestive of polygenic, multifactorial inheritance.8 Concordance in monozygotic twins is 23%,6 indicating that both genetic and nongenetic (presumably environmental) factors play major roles in disease pathogenesis.
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Almost all studies of vitiligo genetics have focused on GV. Several genes involved in immune function, including loci in the MHC, CTLA4, PTPN22, IL10, MBL2, and NALP1 (NLRP1), have been implicated in susceptibility to GV on the basis of genetic linkage or association studies.7 A recent, very large genome-wide association (GWA) study of European Caucasian GV patients and families identified at least ten different loci that contribute to GV risk.13 Seven of these GV susceptibility loci have also been associated with other autoimmune diseases [(1) HLA class I, (2) HLA class II, (3) PTPN22, (4) LPP, (5) IL2RA, (6) UBASH3A, and (7) C1QTNF6], two loci encode proteins involved in immune function [(1) RERE and (2) GZMB], and another locus, TYR, encodes tyrosinase, a key enzyme of melanin biosynthesis and the major GV autoantigen.
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Segmental vitiligo (SV) appears to be genetically distinct from GV. Its generally sporadic occurrence and unilateral distribution have led to ...