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Linkage and association of HLA class II genes with vitiligo in a Dutch population
M Zamani1, M Spaepen, S S Sghar
1Centre for Human Genetics, University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Background:
Serological typing of HLA has shown discrepancies in HLA associations with vitiligo in different ethnic populations.
Objectives:
To perform genotyping of HLA class II genes on a Dutch vitiligo population in order clearly to identify susceptible and protective HLA alleles in vitiligo.
Methods:
HLA typing was carried out by amplifying genomic DNA by polymerase chain reaction (PCR) followed by dot-blot hybridization with sequence-specific oligonucleotides (SSO). Fifty Dutch vitiligo probands, and their parents (150 individuals) and 204 healthy controls were studied.
Results:
Family-based case-control association studies and linkage disequilibrium analysis showed the linkage and association of DRB4*0101 allele with vitiligo (P(c) = 0.0016, relative risk = 2.21). The family-based association study also provided evidence for linkage and association of DQB1*0303 allele with vitiligo (chi(2) = 7.36, P = 0.006). We measured the clinical relevance of the test by calculating the prevalence corrected positive predictive values (PcPPV). The PcPPV of disease for the DRB4*0101 allele was 0.017 and for the DRB4*0101/0101 genotype was 0.0358. In other words, a DRB4*0101/0101 genotype carries a 3.58% risk of developing vitiligo.
Conclusions:
Both DRB4*0101 and DQB1*0303 alleles provide significant susceptibility for vitiligo.