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Increased Tumor Necrosis Factor (TNF)-? and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.

ABSTRACT: Tumor Necrosis Factor (TNF)-?, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-?. Genetic polymorphisms in the promoter region of TNF-? are involved in the regulation of its expression. The present study explores TNF-? promoter polymorphisms and correlates them with TNF-? transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-? transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-? transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-? levels in vitiligo patients. Analysis of TNF-? levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-?. Also, the TNF-? levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-? promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-? transcript and protein levels in individuals with susceptible haplotypes advocates the crucial role of TNF-? in autoimmune pathogenesis of vitiligo.

SUBMITTER: Laddha NC

PROVIDER: S-EPMC3527546 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.

Laddha Naresh C NC Dwivedi Mitesh M Begum Rasheedunnisa R

PloS one 20121220 12

Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with ...[more]

PMID: 23284977

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Project description:BackgroundThe tumour necrosis factor-α (TNF-α) gene plays an important role in the host immune response, which will influence the development and clearance of cancer. Polymorphism of the TNF-α promoter region is considered to influence its transcription and be a risk factor for tumorigenesis. In the current study, we evaluated the role of TNF-α promoter region polymorphisms in susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer (CC).MethodsA total of 2732 subjects, including 1173 healthy controls, 579 patients with CIN and 980 patients with CC in a Chinese Han population, were selected for the current study. Five SNPs in the TNF-α promoter, rs1799964 (-1031 C>T), rs1800630 (-863 A>C), rs1799724 (-857 C>T), rs1800629 (-308 A>G) and rs361525 (-238 A>G), were selected and genotyped using TaqMan Assays. The association of these SNPs with CIN and cervical cancer was evaluated among healthy controls, CIN and CC patients.ResultsThe frequency distribution of rs1800629 and rs361525 alleles was significantly different between the CC group and the control group (P=0.009 and P=0.002). The rs1800629 A allele was found to be a protective factor for CC (OR=0.72; 95% CI=0.56-0.92). The rs361525 A allele was found to be a risk factor for CC (OR=1.69; 95% CI=1.21-2.38). After pathological subtyping of CC, the allele distribution of rs1800629 and rs361525 were both significantly different between the cervical squamous cell carcinoma and control groups (P=0.002 and P<0.001). The rs1800629 A allele was protective factor for cervical squamous cell carcinoma (OR=0.66; 95% CI=0.50-0.86). The rs361525 A allele was a risk factor for cervical squamous cell carcinoma (OR=1.87; 95% CI=1.32-2.65). Moreover, the genotypic frequency of rs361525 was significantly different between cervical cancer stage I and stage II (P=0.003).ConclusionThe rs1800629 and rs361525 in the TNF-α promoter are associated with susceptibility to CC in the Chinese Han population.

Dataset Information

Increased Tumor Necrosis Factor (TNF)-? and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.

Publications

Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.

Similar Datasets

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