title: Involvement of interferon-gamma genetic variants and intercellular adhesion molecule-1 in onset and progression of generalized vitiligo.
abstract: Interferon-gamma (IFN-γ) is a paracrine inhibitor of melanocytes and genetic variability due to intron 1 polymorphisms in IFNG has been reported to be associated with increased risk for several autoimmune diseases. The aim of present study was to determine whether intron 1 +874A/T (rs2430561) and CA microsatellite (rs3138557) polymorphisms in IFNG are associated with generalized vitiligo (GV) susceptibility and expression of IFNG and intercellular adhesion molecule-1 (ICAM1) affects the disease onset and progression. Here we report that IFNG CA microsatellite but not +874A/T may be a genetic risk factor for GV; however, +874T allele plays a crucial role in increased expression of IFNG mRNA and protein levels which could affect the onset and progression of the disease. Active GV patients showed increased IFNG levels compared to stable GV patients. The genotype-phenotype analysis revealed that IFNG expression levels were higher in patients with +874 TT genotypes and 12 CA repeats. Patients with the early age of onset showed higher IFNG expression and female GV patients showed higher IFNG and ICAM1 expression implicating gender biasness and involvement of IFN-γ in early onset of the disease. Moreover, the increased IFN-γ levels in patients lead to increased ICAM1 expression, which could be a probable link between cytokines and T-cell involvement in pathogenesis of GV.
authors.affiliation: 1 Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda , Vadodara, India .
authors.forename: Mitesh
authors.initials: M
authors.lastname: Dwivedi
authors.forename: Naresh C
authors.initials: NC
authors.lastname: Laddha
authors.forename: Kriti
authors.initials: K
authors.lastname: Shah
authors.forename: Bela J
authors.initials: BJ
authors.lastname: Shah
authors.forename: Rasheedunnisa
authors.initials: R
authors.lastname: Begum
mesh_terms: D018450:Disease Progression; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012727:Sex Characteristics; D014820:Vitiligo / Q000235:genetics* / Q000473:pathology
chemical_list: C573415:IFNG protein, human; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma