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

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 l...

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Autores principales:	Naresh C Laddha, Mitesh Dwivedi, Rasheedunnisa Begum
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/98aa392250fa4b2180bd4f6163378ba8
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spelling	oai:doaj.org-article:98aa392250fa4b2180bd4f6163378ba82021-11-18T08:04:00ZIncreased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.1932-620310.1371/journal.pone.0052298https://doaj.org/article/98aa392250fa4b2180bd4f6163378ba82012-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284977/?tool=EBIhttps://doaj.org/toc/1932-6203Tumor 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 TNF-α 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-α 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-α 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-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α 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-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates the crucial role of TNF-α in autoimmune pathogenesis of vitiligo.Naresh C LaddhaMitesh DwivediRasheedunnisa BegumPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e52298 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naresh C Laddha Mitesh Dwivedi Rasheedunnisa Begum Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.
description	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 TNF-α 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-α 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-α 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-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α 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-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates the crucial role of TNF-α in autoimmune pathogenesis of vitiligo.
format	article
author	Naresh C Laddha Mitesh Dwivedi Rasheedunnisa Begum
author_facet	Naresh C Laddha Mitesh Dwivedi Rasheedunnisa Begum
author_sort	Naresh C Laddha
title	Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.
title_short	Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.
title_full	Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.
title_fullStr	Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.
title_full_unstemmed	Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.
title_sort	increased tumor necrosis factor (tnf)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/98aa392250fa4b2180bd4f6163378ba8
work_keys_str_mv	AT nareshcladdha increasedtumornecrosisfactortnfaanditspromoterpolymorphismscorrelatewithdiseaseprogressionandhighersusceptibilitytowardsvitiligo AT miteshdwivedi increasedtumornecrosisfactortnfaanditspromoterpolymorphismscorrelatewithdiseaseprogressionandhighersusceptibilitytowardsvitiligo AT rasheedunnisabegum increasedtumornecrosisfactortnfaanditspromoterpolymorphismscorrelatewithdiseaseprogressionandhighersusceptibilitytowardsvitiligo
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Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo.

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