HLA class II haplotype DRB1*04–DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset

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Abstract
Summary: Generalized vitiligo is a common autoimmune disorder characterized by white patches of skin and overlying hair caused by loss of pigment‐forming melanocytes from involved areas. Familial clustering of vitiligo is not uncommon, and patients and their relatives are at increased risk for a specific complex of other autoimmune diseases. Compared with sporadic vitiligo, familial vitiligo is characterized by earlier disease onset and greater risk and broader repertoire of autoimmunity, suggesting a stronger genetic component, and perhaps stronger associations with specific alleles. To determine whether the major histocompatibility complex (MHC) contributes to the familial clustering of vitiligo and vitiligo‐associated autoimmune/autoinflammatory diseases, we performed case–control and family‐based association analyses of HLA class II‐DRB1 and ‐DQB1 alleles and haplotypes in affected probands and their parents from 76 European‐American Caucasian families with familial vitiligo. Affected probands showed a significantly increased frequency of DRB1*04–DQB1*0301 and a significantly decreased frequency of DRB1*15–DQB1*0602 compared with a large sample of reference chromosomes. Family‐based association analyses confirmed these results. Probands with DRB1*04–DQB1*0301 developed vitiligo an average of 13.32 yr earlier than probands with DRB1*15–DQB1*0602. Overall, our results indicate that specific MHC‐linked genetic variation contributes to risk of familial vitiligo, although HLA does not completely explain familial clustering of vitiligo‐associated autoimmune/autoinflammatory diseases.