Correlation of increased MYG1 expression and its promoter polymorphism with disease progression and higher susceptibility in vitiligo patients.

BACKGROUND:MYG1 (Melanocyte proliferating gene 1 or C12orf10) -119C/G promoter and Arg4Gln structural polymorphisms have a functional impact on its regulation. The promoter polymorphism was shown to be associated with vitiligo in Caucasian population. OBJECTIVE:The present study explores MYG1 polymorphisms and correlates them with MYG1 mRNA expression, disease onset and progression in vitiligo patients. METHODS:Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping of MYG1 -119C/G promoter (rs1465073) and 11-12AA/GC structural polymorphisms (rs1534284-rs1534283; Arg4Gln) in 846 vitiligo patients and 726 age-matched unaffected controls. MYG1 mRNA levels were assessed in whole blood of 166 patients and 175 controls by MYG1 -119C/G promoter polymorphism was found to be in significant association with vitiligo being 'G' allele prevalent in patients. However, 11-12AA/GC structural polymorphism was prevalently monogenic in patients and controls with only MYG1 GC (4Arg) allele being present. Significant increase in MYG1 mRNA expression was observed in vitiligo patients compared to controls. The MYG1 mRNA expression was increased in patients with active and generalized vitiligo as compared to stable and localized vitiligo. MYG1 mRNA expression was increased in patients with susceptible -119 GG genotype compared to controls. Also, patients with susceptible -119 GG genotype had early age of onset of vitiligo. Moreover, patients with age groups 1-20 years and 21-40 years showed increased expression of MYG1 mRNA compared to those of controls. Female patients showed significant increase in MYG1 mRNA and early age of onset of vitiligo compared to male patients. CONCLUSION:The present study suggests that MYG1 -119C/G promoter polymorphism may be a genetic risk factor for susceptibility and progression of vitiligo. The up-regulation of MYG1 transcript in patients with susceptible -119GG genotype advocates the crucial role of MYG1 in autoimmune pathogenesis of vitiligo.

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