Meta-analysis for association of TNFA-308(G &gt; A) SNP with vitiligo susceptibility

Giri, Prashant S.; Begum, Rasheedunnisa; Dwivedi, Mitesh

doi:10.1016/j.gene.2021.146027

Cited by 15 publications

(10 citation statements)

References 42 publications

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“…The main keywords were “Tregs vitiligo,” “vitiligo,” “regulatory T cells,” “Treg,” “Treg cells number,” “Treg cells frequency,” “suppressive function,” “FOXP3,” “Forkhead box P3,” “IL-10,” “interleukin 10,” “transforming growth factor beta,” and “TGF- β .” The detailed search strategy is mentioned in Table S1 . “The study protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines” (Table S2 ) [ 38 , 39 ]. The studies were searched on the database for four different times independently by three investigators.…”

Section: Methodsmentioning

confidence: 99%

“…“The NOS criteria were graded on a scale of 0 to 9, and three important criteria were included: (1) evaluation, (2) selection, and (3) ascertaining the outcome. Studies with a NOS score of five or higher were deemed as high-quality studies, while those with a lower score were deemed low-quality studies” [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

“…The detailed search strategy is mentioned in Table S1. "The study protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines" (Table S2) [38,39]. The studies were searched on the database for four different times independently by three investigators.…”

Section: Methodsmentioning

confidence: 99%

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Meta-Analysis of Alterations in Regulatory T Cells’ Frequency and Suppressive Capacity in Patients with Vitiligo

Giri

Mistry

Dwivedi

2022

Journal of Immunology Research

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Vitiligo is a noncontagious autoimmune skin depigmenting disease. Regulatory T cells (Tregs) play a key role in maintaining peripheral tolerance; however, Tregs' number, suppressive function, and associated suppressive molecules (FOXP3, IL-10, and TGF- β ) are found to be reduced in vitiligo patients. Although, the role of Tregs in vitiligo pathogenesis is well established, there are several contrary findings which suggest a controversial role of Tregs in vitiligo. Therefore, to clarify the role of Tregs in vitiligo pathogenesis, we aimed to study Tregs' frequency, suppressive capacity, and associated suppressive molecules (FOXP3, IL-10, and TGF- β ) in vitiligo patients through meta-analysis approach. A total of 30 studies involving 1223 vitiligo patients and 1109 controls were included in the study. Pooled results from our meta-analysis suggested significantly reduced Treg cells' frequency in vitiligo patients ( p = 0.002). Interestingly, Tregs' suppressive capacity was also significantly reduced in vitiligo patients ( p = 0.0002); specifically, Treg-mediated suppression of CD8 + T cells was impaired in vitiligo patients ( p < 0.00001). Moreover, FOXP3, a key Tregs' transcription factor, was significantly reduced in blood and skin of vitiligo patients ( p < 0.00001). Intriguingly, the FOXP3 expression was significantly reduced in the lesional skin as compared to perilesional and nonlesional skin ( p = 0.007 and p = 0.04). Furthermore, the expression of key Treg-associated suppressive cytokines IL-10 and TGF- β were significantly reduced in vitiligo patients ( p = 0.0005 and p = 0.01). The disease activity-based analysis suggested for reduced Tregs' frequency and FOXP3 expression in active vitiligo patients ( p = 0.05 and p = 0.01). We also studied the effect of microRNA-based treatment, narrow band–UVB phototherapy, and Treg-associated treatments on Tregs' frequency, FOXP3, and IL-10 expression. Interestingly, we found increased Tregs' frequency, FOXP3, and IL-10 expression after the treatment ( p = 0.007, p < 0.0001, and p = 0.002). Overall, our meta-analysis suggests that the Tregs play a crucial role in pathogenesis and progression of vitiligo, and hence, Treg-based therapeutic interventions could be effective in vitiligo patients.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Meta-Analysis of Alterations in Regulatory T Cells’ Frequency and Suppressive Capacity in Patients with Vitiligo

Giri

Mistry

Dwivedi

2022

Journal of Immunology Research

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“…Tumor necrosis factor (TNF)-α-308 G/A gene polymorphism was the most investigated in vitiligo patients. The recent meta-analysis of Giri et al [38] suggested the involvement of susceptible 'A' allele with vitiligo susceptibility in overall population, whereas the previous studies failed to reveal that TNF-α-308 G/A polymorphism is a genetic risk factor for vitiligo [39,40].…”

Section: Plos Onementioning

confidence: 96%

Gene polymorphisms and serum levels of BDNF and CRH in vitiligo patients

et al. 2022

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Background Vitiligo is one of the most common hypomelanoses, in which the destruction of functioning melanocytes causes depigmentation of the skin, hair and mucous membranes. The genes encrypting brain-derived neurotrophic factor (BDNF) and corticotropin releasing hormone (CRH) might be the conceivable contributors to the development of vitiligo. This study was aimed at investigation of the serum levels of BDNF and CRH as well as their selected single nucleotide polymorphisms (SNPs) in vitiligo patients in comparison with the healthy controls. Methods The cross-sectional study was carried out between October 2020 and June 2021 in 93 vitiligo patients (age range from 23 to 48 years) and 132 healthy controls (age range from 24 to 52 years). The psychological status of study participants was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) scale. Serum levels of BDNF and CRH were measured with the help of a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Genotyping for the rs11030094 polymorphism of the BDNF gene and for the rs242924 polymorphism of the corticotropin releasing hormone receptor 1 (CRH-R1) gene was performed by a real-time polymerase chain reaction (PCR). Results There was a significant relationship between the CRH-R1 rs242924 and BDNF rs11030094 polymorphisms and vitiligo. Moreover, serum levels of neurotransmitters differed significantly between vitiligo and control groups and were associated with the CRH-R1 rs242924 and BDNF rs11030094 SNPs. Conclusions Our findings demonstrated the association between CRH-R1 rs242924 and BDNF rs11030094 polymorphisms and vitiligo. Further studies need to be carried out in vitiligo patients to confirm the results observed.

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“…Furthermore, if they remain unchecked, these autoreactive T cells can lead to granzyme and FAS-FASL-mediated melanocyte destruction, leading to GV pathogenesis [4][5][6][7][8]. Additionally, our previous studies have found the role of inflammatory cytokines IFN-γ and TNF-α in melanocyte destruction [6,[9][10][11].…”

Section: Introductionmentioning

confidence: 98%

Decreased GZMB, NRP1, ITPR1, and SERPINB9 Transcripts Lead to Reduced Regulatory T Cells Suppressive Capacity in Generalized Vitiligo Patients

Giri

Bharti²,

Dwivedi

2022

Journal of Immunology Research

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Generalized vitiligo (GV) is an autoimmune skin disease characterized by bilateral white patches over the entire body. Regulatory T cells (Tregs) maintain peripheral tolerance; however, they are found to be reduced in numbers and function in vitiligo patients. The exact mechanism for reduced Treg suppressive capacity is unknown. Therefore, we aimed to assess transcript levels of Tregsassociated immunosuppressive genes (GZMB, NRP1, PDCD1, FASLG, and TNFRS18), regulatory molecules of Tregs suppressive function (SERPINB9, ITPR1, and UBASH3A), and Treg-associated transcription factors (GATA2, GATA3, RUNX1, STAT3, and STAT5) in 52 GV patients and 48 controls by real-time PCR (qPCR). We found significantly reduced GZMB, NRP1, SERPINB9, and ITPR1 transcripts in GV Tregs compared to controls (p = 0:03, p = 0:023, p = 0:0045, and p < 0:0001, respectively). There were 0.44-, 0.45-, 0.32-, and 0.54-fold decrease in GZMB, NRP1, SERPINB9, and ITPR1 transcripts in GV Tregs. Additionally, disease activity and severity-based analyses revealed significantly decreased GZMB (p = 0:019 and 0.034), SERPINB9 (p = 0:031 and p = 0:035), and ITPR1 (p = 0:0003 and p = 0:034) transcripts in active vitiligo and severe GV patients' Tregs. Interestingly, we found a positive correlation for ITPR1 with GZMB (r = 0:45, p = 0:0009) and SERPINB9 (r = 0:52, p = 0:001) transcripts in GV Tregs. Moreover, we found positive correlation for percentage Treg mediated suppression of CD4 + and CD8 + T cells with ITPR1 (r = 0:54; r = 0:49), GZMB (r = 0:61; r = 0:58), NRP1 (r = 0:55; r = 0:52), and SERPINB9 (r = 0:56; r = 0:48) in GV Tregs. Further, calcium treatment of Tregs resulted into significantly increased ITPR1, SERPINB9, and GZMB transcripts in GV Tregs (p = 0:023, p = 0:0345, p = 0:02). Overall, our results for the first time revealed the crucial role of GZMB, NRP1, SERPINB9, and ITPR1 transcripts in decreased Treg suppressive capacity leading to GV pathogenesis, progression, and severity. In addition, our study highlighted that ITPR1 might be linked with decreased GZMB and NRP1 expression in GV Tregs. Moreover, our study for the first time suggest that increased SERPINB9 transcripts may lead to endogenous granzyme B-mediated Tregs apoptosis, and calcium treatment of Tregs may improve the Treg suppressive capacity. These findings may further aid in development of Treg-based therapeutics for GV.

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Meta-analysis for association of TNFA-308(G > A) SNP with vitiligo susceptibility

Cited by 15 publications

References 42 publications

Meta-Analysis of Alterations in Regulatory T Cells’ Frequency and Suppressive Capacity in Patients with Vitiligo

Meta-Analysis of Alterations in Regulatory T Cells’ Frequency and Suppressive Capacity in Patients with Vitiligo

Gene polymorphisms and serum levels of BDNF and CRH in vitiligo patients

Decreased GZMB, NRP1, ITPR1, and SERPINB9 Transcripts Lead to Reduced Regulatory T Cells Suppressive Capacity in Generalized Vitiligo Patients

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