Association of TNF-α-308(GG), IL-10−819(TT), IL-10−1082(GG) and IL-1R1+1970(CC) genotypes with the susceptibility and progression of leprosy in North Indian population

Tarique, Mohd; Naqvi, Raza Ali; Santosh, K.V.; Kamal, Vineet Kumar; Khanna, Neena; Rao, Nageswara S. V.

doi:10.1016/j.cyto.2015.01.014

Cited by 26 publications

(20 citation statements)

References 22 publications

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“…We found a total of 11 studies that evaluated the influence of IL10 polymorphisms and leprosy published between 2001–2015; all of them were case-control studies that were conducted in Brazilian [ 7 , 18 – 20 ], Indian [ 21 – 23 ], Malawian [ 24 ], Mexican [ 25 ], Colombian [ 26 ] and Chinese [ 27 ] populations. The studies from Malhotra et al, 2005 and Aggarwal et al, 2011 presented partially overlapping population, therefore we excluded from meta-analysis the data from Malhotra et al 2005 [ 21 ] corresponding to the -819 and -592 polymorphisms.…”

Section: Resultsmentioning

confidence: 99%

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis

et al. 2015

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Leprosy is a chronic infectious disease that depends on the interplay of several factors. Single nucleotide polymorphisms (SNPs) in host immune related genes have been consistently suggested as participants in susceptibility towards disease. Interleukin-10 (IL-10) is a crucial immunomodulatory cytokine in mycobacterial pathogenesis and especially the -819C>T SNP (rs1800871) has been tested in several case-control studies indicating association with leprosy risk, although a recent consensus estimate is still missing. In this study, we evaluated the association of the -819C>T SNP and leprosy in two new Brazilian family-based populations. Then, we performed meta-analysis for this polymorphism summarizing published studies including these Brazilian family-based groups. Finally, we also retrieved published studies for other distal and proximal IL10 polymorphisms: -3575 T>A (rs1800890), -2849 G>A (rs6703630), -2763 C>A (rs6693899), -1082 G>A (rs1800896) and -592 C>A (rs1800872). Results from meta-analysis supported a significant susceptibility association for the -819T allele, with pooled Odds Ratio of 1.22 (CI = 1.11–1.34) and P-value = 3x10–5 confirming previous data. This result remained unaltered after inclusion of the Brazilian family-based groups (OR = 1.2, CI = 1.10–1.31, P-value = 2x10–5). Also, meta-analysis confirmed association of -592 A allele and leprosy outcome (OR = 1.24, CI = 1.03–1.50, P-value = 0.02). In support of this, linkage disequilibrium analysis in 1000 genomes AFR, EUR, ASN and AMR populations pointed to r2 = 1.0 between the -592C>A and -819C>T SNPs. We found no evidence of association for the other IL10 polymorphisms analyzed for leprosy outcome. Our results reinforce the role of the -819C>T as a tag SNP (rs1800871) and its association with leprosy susceptibility.

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Section: Resultsmentioning

confidence: 99%

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis

et al. 2015

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“…IL-10, a cytokine with immunosuppressive properties secreted by monocyte and lymphocyte lineages, has been demonstrated to play roles in the development of L-lep (15,96). Variant−819 C/T (rs1800871) in the promoter region of gene IL10 was repeatedly found to be associated with leprosy (142,147). And two meta analyses focusing on IL10 variants both confirmed the significant susceptibility association between−819 C/T (rs1800871) and leprosy (148,149).…”

Section: Roles Of Cytokine Gene Polymorphisms In Leprosymentioning

confidence: 94%

“…This region encodes pleiotropic cytokines TNF and LTA, which have various immune regulatory functions. Moreover, the most frequently involved SNP of TNF in infectious diseases, TNF-308 G>A (rs1800629), has been widely studied in leprosy with different ethnicities, including Nepalese, Brazilians, and Indians (115,141,142). However, these studies obtained inconsistent results for the association of TNF-308 G>A with leprosy, which inspired a meta-analysis of 14 studies on this topic (143).…”

Section: Roles Of Cytokine Gene Polymorphisms In Leprosymentioning

confidence: 99%

Advances in the Immunology and Genetics of Leprosy

Liu

Zhang

2020

Front. Immunol.

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“…Of late, our group has been made tremendous efforts to understand the overt immune derangements associated with progression of the leprosy. [1] We showed that disease progression in leprosy patients results in M. leprae-infected cholesterol-depleted immature macrophages secreting high levels of TGF-β, which eventually led to induction of competitively fit CD4 + CD25 + FoxP3 + T regs [2] in MB patients. [3] We also observed an increase in CD4 + TCR γδ + cells with the disease progression.…”

Section: Introductionmentioning

confidence: 99%

CD4⁺TCRγδ⁺FoxP3⁺ cells: An unidentified population of immunosuppressive cells towards disease progression leprosy patients

Tarique

Naqvi

Ali

et al. 2017

Experimental Dermatology

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This study, for the first time, reveals the role of M. leprae‐specific CD4+TCRγδ+FoxP3+ cells in the progression and pathogenesis of leprosy. Co‐culture with CD4+CD25− cells suggested the immunosuppressive nature of CD4+TCRγδ+ cells in dose‐dependent manner. Isolation of CD4+TCRγδ+ cells from leprosy patients and then culture in presence of M. leprae cell wall antigens (MLCwA) along with TGF β, IPP and IL‐2 suggested that these cells are M. leprae specific. TGF‐β‐mediated SMAD3 signalling was turned out to be major factor towards the expression of FoxP3 in these cells. SMAD3 silencing during induction of these cells barely showed the induction of FoxP3. High density of SMAD3 binding at TGFβRII in CD4+TCRγδ+FoxP3+ furthermore suggested the TGF‐β‐directed SMAD3 signalling in these cells. Taken together the above data, we can conclude that CD4+TCRγδ+FoxP3+ cells possess the potential to track the severity of the disease in leprosy patients.

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Association of TNF-α-308(GG), IL-10−819(TT), IL-10−1082(GG) and IL-1R1+1970(CC) genotypes with the susceptibility and progression of leprosy in North Indian population

Cited by 26 publications

References 22 publications

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis

Advances in the Immunology and Genetics of Leprosy

CD4⁺TCRγδ⁺FoxP3⁺ cells: An unidentified population of immunosuppressive cells towards disease progression leprosy patients

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Association of TNF-α-308(GG), IL-10−819(TT), IL-10−1082(GG) and IL-1R1+1970(CC) genotypes with the susceptibility and progression of leprosy in North Indian population

Cited by 26 publications

References 22 publications

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis

Advances in the Immunology and Genetics of Leprosy

CD4+TCRγδ+FoxP3+ cells: An unidentified population of immunosuppressive cells towards disease progression leprosy patients

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Product

Resources

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CD4⁺TCRγδ⁺FoxP3⁺ cells: An unidentified population of immunosuppressive cells towards disease progression leprosy patients