title: HLA class II haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset.
abstract: 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.
authors.affiliation: Human Medical Genetics Program, University of Colorado at Denver and Health Sciences Center, Aurora, USA.
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fain
authors.forename: Sunanda R
authors.initials: SR
authors.lastname: Babu
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Bennett
authors.forename: Richard A
authors.initials: RA
authors.lastname: Spritz
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000378:metabolism; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D014820:Vitiligo / Q000235:genetics / Q000276:immunology
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins