Contribution of HLA Class II Genes, DRB4*01:01, DRB1*07:01, and DQB1*03:03:2 to Clinical Features of Vitiligo Disease in Iranian Population

Background: Vitiligo is a multifactorial depigmentation condition, which is due to skin melanocyte destruction. The increased expression of HLA class II genes in patients with pre-lesions of Vitiligo suggests an important role for the participation of immune response in the Vitiligo development. Recent studies progressively focused on HLA-DRB1 and DQB1 genes. In this study, we have evaluated the association and role of HLA-DRB4*01:01, -DRB1*07:01, and -DQB1*03:03:2 genes in different clinical subtypes of Vitiligo in the Iranian population.Methods: First, Genomic DNA from peripheral blood of 125 unrelated Vitiligo patients and 100 unrelated healthy controls were extracted through salting-out method. Then, HLA CLASS II genotyping were performed using sequence-specific primer PCR method. Finally, the clinical relevance of the testing for these genotypes were evaluated by applying the PcPPV (prevalence-corrected positive predictive value) formula.Results: Our results indicated the positive associations of DRB4*01:01 and DRB1*07:01 allelic genes with early-onset Vitiligo (P= 0.024 and 0.022, respectively). The DRB4*01:01 also showed a strong protection against late-onset Vitiligo (P= 0.0016, RR=0.360). Moreover, our data revealed that the DRB1*07:01 increases the susceptibility to Sporadic Vitiligo (P=0.030, RR=1.702). Furthermore, our findings proposed that elevated vulnerability of Vitiligo patients due to DRB4*01:01 and DRB1*07:01 alleles may be is correlated with the presence of amino acid Arginine at position 71 at pocket 4 on the antigen-binding site of the HLA-DRB1 receptor.Conclusion: Our findings on different subtypes of Vitiligo suggest that, despite a more apparent autoimmune involvement, a non-autoimmune nature for the etiology of Vitiligo could also be considered.