Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo

Abstract

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

Interferon‐γ and interleukin‐12 production in relation to gene polymorphisms in bacillus Calmette–Guérin osteitis

“…The functionality of the IFNγ rs2430561 and rs35314021 SNP has been well documented based on measurements of IFN‐γ in serum of patients with leishmaniasis or vitiligo . In addition, the major allele T in IFNγ rs2430561, which we used in the present study, was associated with expression of IFNγ mRNA and further with higher serum IFN‐γ concentration . In the Finnish publicly available population‐based data, the IFNγ rs2430561 and rs35314021 SNP are completely identical in terms of the occurrence of the wild, the variant heterozygous and the variant homozygous genotypes, which was documented also in the present study.…”

“…In addition, the vitiligo patients with TT or AT rs2430561 genotypes had higher serum IFN‐γ concentration than controls or those vitiligo patients who had the homozygous variant AA genotype . Likewise, in another study, the presence of the major allele T in the rs2430561 SNP was associated with overexpression of IFNγ mRNA and elevated serum IFN‐γ concentration in adults with vitiligo …”

“…The functionalities of the IFNγ rs2430561 and rs35314021 SNP have been documented in vitiligo and leishmaniasis patients and in healthy controls . IFNγ expression was higher in adults with vitiligo than in controls, if the patients had the wild TT genotype in the rs2430561 SNP or at least 12 CA (GT, reverse) microsatellite repeats in the rs35314021 SNP .…”

“…The coding region of IFNγ is invariant with no reported polymorphisms, but there are two well‐known single‐nucleotide polymorphisms (SNP) in the non‐coding region of IFNγ : +874T>A SNP (rs2430561) and CA (or GT depending on the direction of code reading) microsatellite (rs138557) . These SNP are functional, regulating IFNγ mRNA expression in cells and IFN‐γ concentration in serum …”

The IFNG rs1861494 Single Nucleotide Polymorphism Is Associated with Protection against Tuberculosis Disease in Argentina

“…Here, by using a case-control study, we reported an association between the AA and AG genotype of the IFNG rs1861494 SNP with tuberculosis resistance in Argentina, indicating that only one copy of the A allele is enough to confer protection against the disease in our population. In particular, the IFNG rs1861494 SNP was a good candidate to study the genetic association because it has been widely validated (sequenced in 1000 Genome project, Genotyped by HapMap project, and multiple, independent submissions to the ref SNP cluster) [ 33 ] and associated with different diseases immunoglobulin A (IgA) nephropathy, vitiligo, inflammatory bowel disease, leprosy, tuberculosis, between others) [ 28 , 34 , 35 , 36 , 37 ].…”