Association Study Of HLA Class Ⅱ Gene With Vitiligo And Its Clinical Features In Chinese Han Population

Background:Vitiligo is a common depigmentary disorder resulting from selective destruction of melanocytes in the skin and hair, with diverse prevalence rates ranging from0.1%to2.9%in different geographic regions and ethnic groups. Although non-fatal, vitiligo could cause severe negative psychosocial impact on the individuals affected. Vitiligo usually begins in childhood or young adulthood, with approximately half of the patients having onset before the age of20years. Therefore, patients with onset at20years or younger were classified as early-onset vitiligo, while patients with onset older than20years were classified as late-onset vitiligo. Clinical and epidemiological investigations indicated that vitiligo might follow a pattern of polygenetic or multifactorial inheritance, and several hypotheses of which most are unproved so far, have been proposed to explain the pathogenesis of vitiligo, including self-destructive, biochemical, neural, autoimmune and genetic hypotheses. In the past decades, the autoimmune hypothesis had received the most attention based partly on the frequent occurrence of other autoimmune diseases in vitiligo patients and their relatives including autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anaemia, Addison’s disease and systemic lupus erythematosus. The human leucocyte antigen (HLA) is now recognized as a major contributing factor for susceptibility to a variety of autoimmune diseases, and numerous associations with vitiligo have focused on the HLA system. Most of them reported multiple HLA class II alleles to be associated with vitiligo in different populations; however, a few studies had consistent association evidence, which might be explained by weak genetic effects or complex gene-gene or gene-environmental interactions, population stratification or genetic differences between populations. Of HLA class II alleles, DRB1*07has consistently shown a positive association with vitiligo in Chinese Han population through reanalysis of previous studies. Interestingly, abnormal expression of HLA-DR in perilesional epidermis has also been reported and was suggested to contribute to HLA class II-restricted melanocyte killing. Recently, several studies have further suggested that HLA class II alleles/haplotypes have been inclined towards patients who have earlier-onset age, with autoimmune diseases or with family history.Objective:(1) To further explore the relationship between HLA class II gene and vitiligo in Chinese Han population.(2) To evaluate the HLA class II gene effect on the clinical features of vitiligo in Chinese Han population.Methods:This study investigated DRB1*07allele distribution in1178unrelated Chinese vitiligo patients and1743healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07positive and DRB1*07negative patients.Results:(1) A significant proportion of patients were DRB1*07positive compared with the control group (40.75%vs.25.83%, OR=1.97,95%CI1.68-2.31, P=2.13×10-17). The DRB1*07positive allele of case and control were0.20and0.13respectively. Of all the patients,480were DRB1*07positive and the remaining698patients were DRB1*07negative. The mean age was25.57±14.45year in DRB1*07positive group and27.43±14.71year in DRB1*07negative group (P=0.031). The gender distribution showed an approximately equal proportion in the two groups (P=0.099).(2) DRB1*07positive patients have an earlier disease onset than DRB1*07negative patients, the median age of onset being17.00±16.00year vs.19.00±18.00year for DRB1*07positive and DRB1*07negative patients respectively (P=0.004).The frequency of early-onset vitiligo was also significantly higher in DRB1*07positive patients than DRB1*07negative patients (65.14%vs.55.59%, P=0.001, OR=1.49,95%CI1.17-1.90).(3) Family history of vitiligo was more common in DRB1*07positive patients than in DRB1*07negative patients. There were30.8%patients with positive family history in DRB1*07positive group, compared with23.6%patients in DRB1*07negative group (OR=1.44,95%CI1.11-1.87, P=0.006).(4) The DRB1*07positive group showed increased frequency of autoimmune diseases compared with DRB1*07negative group (4.0%vs.3.2%), however, the difference did not reach significant level (OR=1.27,95%CI0.68-2.37, P=0.458).Conclusions:(1) The HLA class II gene showed significant association with vitiligo in Chinese Han population.(2) This study confirmed that DRB1*07positive patients had some obvious clinical differences (with earlier-onset age and family history) from DRB1*07negative patients in the Chinese Han population.(3) This study provides evidence that genetic component of autoimmune susceptibility might play a key role in the pathogenesis of some clinical features or subtypes of vitiligo.