Interleukin-4 genetic variants correlate with its transcript and protein levels in patients with vitiligo

Imran, Mohamad; Laddha, Naresh C.; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Jyotsna; Rani, Rajni; Gokhale, Rajesh S.; Sharma, Vinod; Marfatia, Yogesh S; Begum, Rasheedunnisa

doi:10.1111/j.1365-2133.2012.11000.x

Cited by 75 publications

(36 citation statements)

References 38 publications

(44 reference statements)

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“…Recently, we have shown positive association of HLA-A*33:01, HLA-B*44:03, and HLA-DRB1*07:01 with vitiligo patients from North India and Gujarat suggesting an autoimmune link of vitiligo in these cohorts [22]. The genotype-phenotype correlation of CTLA -4 and IL -4 gene polymorphisms also supported the autoimmune pathogenesis of vitiligo in Gujarat population [23],[24], whereas our earlier studies on MBL -2, ACE, PTPN 22 polymorphisms did not show significant association [25]–[27].…”

Section: Discussionmentioning

confidence: 52%

Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

2012

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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.

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Section: Discussionmentioning

confidence: 52%

Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

2012

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“…We have also shown that the three most significant class II region SNPs: rs3096691 (just upstream of NOTCH4), rs3129859 (just upstream of HLA-DRA), and rs482044 (between HLA-DRB1 and HLA-DQA1) are associated with generalized vitiligo in Indian population [29]. The genotype-phenotype correlation of CTLA4, IL4 and TNFA gene polymorphisms also supported the autoimmune pathogenesis of vitiligo in Gujarat population whereas our earlier studies on CAT, GPX, MBL2, ACE, and PTPN22 polymorphisms did not show significant association [30][31][32][33][34][35][36].…”

Section: Discussionmentioning

confidence: 66%

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

Dwivedi

Laddha

Begum

2013

Journal of Dermatological Science

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“…Hernanz et al [68] reported that NPY enhanced the production of IL6 and TNFα in peripheral blood cells. In addition, our previous studies have shown high levels of serum IL4 and TNFα as well as increased mRNA levels in patients with vitiligo compared to controls [62], [63] suggesting that NPY might be involved in the cell-mediated as well as humoral immune mechanisms and plays a crucial role in melanocyte destruction. However, the exact role of NPY in vitiligo pathogenesis is yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

et al. 2014

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BackgroundVitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels.ObjectivesAim of the present study was to explore NPY promoter −399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter −511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo.MethodsPCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B −511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR.ResultsGenotype and allele frequencies for NPY −399T/C, +1128T/C and IL1B −511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001) between patients and controls. ‘TC’ haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001). Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029), in patients with active than stable vitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes.ConclusionOur results suggest that NPY −399T/C, +1128T/C and IL1B −511C/T polymorphisms are associated with vitiligo and IL1B −511C/T SNP influences its transcript levels leading to increased risk for vitiligo in Gujarat population. Up-regulation of IL1B transcript in patients advocates its possible role in autoimmune pathogenesis of vitiligo.

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Interleukin-4 genetic variants correlate with its transcript and protein levels in patients with vitiligo

Cited by 75 publications

References 38 publications

Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

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

Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

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