| Background Vitiligo was a chronic depigmentative skin disease,characterized by milky white macules and achromic or hypochromic patches.Except for skin,multiple body areas in which melanocytes exist could be affected by vitiligo,including hair follicle,mucosa,inner eyes and retina.And the symptoms in this areas might be usually atypical.The prevalence of vitiligo varied among different ethnics and regions.The prevalence of vitiligo in China would be 0.09%to 1.9%and even had a prevalence heterogeneity among geographic regions of China.The exact pathogenesis of vitiligo was still unclear.Although a variety of hypothesis supported the mechanisms of vitiligo onset,such as autoimmune theory,genetic theory,Neurohumoral theory,oxidative stress theory and autocytotoxic theory,these hypothesis would partially explained the pathogenesis of vitiligo.Since the wide application of Genome-Wide Association Study?GWAS?technology,a number of vitiligo susceptible genes/loci were found.In previous study,our group conducted GWASs in vitiligo for twice and multiple susceptible gene/loci were indentified to be associated with vitiligo.The same researches were also carried out in European and Korean populations.So far,more that 58 vitiligo susceptible genes/loci have been identified.However,the most studies did not focused on the genetic profiles in different vitiligo subtypes.In our clinical routines,we usually observed vitiligo patients with special clinical subtypes on which the research would confer special contributions for the disease pathogenesis in different profiles.For examples,we found that cutaneous lesions in some vitiligo patients would be repigmentative spontaneously without any treatments applications.As far as we knew,we did not find any reports or investigations for the phenomenon.In another aspect,although vitiligo might occur in all age stage,the most onset age for the patients would be in adolescent stage.Researchers suggested that vitiligo might be divided in to early onset type and late onset type as the pathogenesis between the two types of vitiligo might be different.However,the definition of age cutoff was controversial.Purpose In this study,we aimed at investigating the genetic characterizations in different vitiligo clinical subtypes.In the section 1,we did epidemiological and genetic study in the cohort of vitiligo repigmentative patients and to investigated the epidemiological characterizations and the genetic features for vitiligo repigmentative tendency.In the section 2,we aimed at investigating whether there were different genetic background in diverse age based vitiligo groups.We would understand the importance of genetic research in clinical subtypes of vitiligo.Method Section 1:We recruited totally 13202 vitiligo patients from multiple hospitals of China.Then we genotyped 26 vitiligo patients with repigmentative tendency and 256 vitiligo patients without repigmentative tendency using Illumina Human 610-Quad SNP genotype chips.Then the SNPs which reached GWAS significance were replicated by Sequenom SNP genotype system in 230 vitiligo patients with repigmentative tendency and 560 vitiligo patients without repigmentative tendency.Section 2:Total 1117 vitiligo patients were rearranged to early onset vitiligo and late onset vitiligo according to the age?20 year-old and 30 year-old?.Then we genotyped each group of vitiligo and 1701 healthy controls using Illumina Human 610-Quad SNP genotype chips.We then compared the results to find whether there were different genetic backgrounds between diverse age based groups.Meanwhile,we further investigated whether the phenomenon which the vitiligo results indicated was universal.Four thousands of psoriasis patients which was averagely rearranged according to the age groups and two thousands of healthy controls were sequenced in MHC region.We meanwhile compared the results to find whether there were different genetic backgrounds between diverse age based groups.The consistent results of vitiligo and psoriasis would be a indicator for explaining that age would influence the genetic profile in dermatological diseases,at least in vitiligo and psoriasis.Results Section 1:?1?Among the total of 7258 vitiligo patients of Han Chinese,two hundred and fifty six patients had repigmentative tendency in the lesion areas without any treatment.The repigmentative tendency rate was estimated as 3.53%.?2?In clinical characterization correlation analysis,we found vitiligo repigmentative tendency was significantly correlated with disease types?sporadic vitiligo vs.focal vitiligo??p=0.015,OR=0.677,95%CI 0.493-0.929?,Keobner phenomenon?0.001,OR=2.061,95%CI 1.443-2.942?and lesion area?sunlight exposure area vs.non-sunlight exposure area,p=0.005,OR=1.775,95%CI 1.182-1.665?.?3?We also did a genetic susceptibility analysis in GWAS-based two step analysis.The result indicated that the SNP rs4903736 was nominally associated with vitiligo repigmentative tendency.Section 2:?1?Susceptible signals for early onset vitiligo were located specifically in the HLA region.Genetic susceptibility for late onset vitiligo had no correlations with HLA region.?2?There were two independent SNPs for the early onset vitiligo:rs3131296(p=3.80×10-17,OR=2.407,95%CI 1.952-2.967)and rs9468925(p=3.51×10-10 OR=0.611,95%CI 0.524-0.714,p-conditional=1.08×10-6,OR-conditional=0.670,95%CI-conditional 0.570-0.787)?3?The SNP rs3131296might be a specific genetic marker for early onset vitiligo.Conclusion Our research disclosed genetic characterizations of clinical subtypes of vitiligo.?1?Vitiligo repigmentative tendency was significantly correlated with sunlight exposure,disease types and Koebner phenomenon,and meanwhile this phenomenon was associated with NRXN3 gene variations.?2?Different genetic backgrounds were found in diverse age based vitiligo and other dermatological diseases,at least in psoriasis.The conclusions above emphasized the significance of genetic research in clinical subtypes of diseases. |
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