The − 308 bp TNF gene polymorphism influences tumor necrosis factor expression in leprosy patients in Bahia State, Brazil

Oliveira, Joyce Moura; Rêgo, Jamile Leão; Santana, Nadja de Lima; Braz, Marcos; Jamieson, Sarra E.; Vieira, Thaillamar Silva; Magalhães, Thaís Lamêgo; Machado, Paulo Roberto Lima; Blackwell, Jenefer M.; Castellucci, Léa

doi:10.1016/j.meegid.2016.01.026

Cited by 8 publications

(13 citation statements)

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“…Most of the SNPs assessed in our study have known biological effects thus allowing a biological interpretation of the observed associations based on increased or reduced gene activity as summarized in Table 2 [ 35 – 47 ]. The associations observed for the TNF (rs1800629 and rs361525) polymorphisms suggest that reduced TNF-α mRNA level and expression of TNF-α was associated with reduced risk of AS [ 48 , 49 ]. This is supported by our haplotype analysis which also suggests that the variant alleles of TNF rs1800629 and rs361525 were associated with reduced risk of AS.…”

Section: Discussionmentioning

confidence: 99%

“…There are aspects of this study which should be interpreted with care. Conflicting results have been reported for the TNF (rs1800629) polymorphism [ 48 , 49 , 65 ]. Furthermore, the TNF polymorphisms, as well as the HLA-B27 locus, are located on chromosome 6, and there is a risk that even a minor linkage disequilibrium could have confounded our results [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the other results this indicate that genetically determined high TNF-driven inflammatory response was associated with reduced risk of AS. TNF rs1800629 Cytokines GA or AA vs GG 0.56 (0.44–0.72) 0.0000047 / 0.00024 -308A increase expression in jurkat cells [ 65 ], reduce mRNA level in PBMC and serum [ 48 ] or no association was found [ 49 ] Reduced TNF-α mRNA level was associated with reduced risk of AS. This could indicate that genetically determined high TNF-driven inflammatory response was associated with increased risk of AS.…”

Section: Methodsmentioning

confidence: 99%

“… OR Odds ratio a OR was calculated for each haplotype combination by using the haplotype 11 as reference group b The variant allele of TNF -238A rs361525A G > A has been shown to reduce expression of TNF-α [ 49 ] c The variant allele of TNF -308A rs1800629 G > A has been shown to reduce mRNA level [ 48 ] …”

Section: Methodsmentioning

confidence: 99%

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Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

et al. 2018

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BackgroundAnkylosing spondylitis (AS) results from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the heritability of AS.MethodsUsing a candidate gene approach in this case-control study, 51 mainly functional single nucleotide polymorphisms (SNPs) in genes regulating inflammation were assessed in 709 patients with AS and 795 controls. Data on the patients with AS were obtained from the DANBIO registry where patients from all of Denmark are monitored in routine care during treatment with conventional and biologic disease modifying anti-rheumatic drugs (bDMARDs).The results were analyzed using logistic regression (adjusted for age and sex).ResultsNine polymorphisms were associated with risk of AS (p < 0.05). The polymorphisms were in genes regulating a: the TNF-α pathway (TNF -308 G > A (rs1800629), and − 238 G > A (rs361525); TNFRSF1A -609 G > T (rs4149570), and PTPN22 1858 G > A (rs2476601)), b: the IL23/IL17 pathway (IL23R G > A (rs11209026), and IL18–137 G > C (rs187238)), or c: the NFkB pathway (TLR1 743 T > C (rs4833095), TLR4 T > C (rs1554973), and LY96–1625 C > G (rs11465996)).After Bonferroni correction the homozygous variant genotype of TLR1 743 T > C (rs4833095) (odds ratios (OR): 2.59, 95% confidence interval (CI): 1.48–4.51, p = 0.04), and TNFRSF1A -609 G > T (rs4149570) (OR: 1.79, 95% CI: 1.31–2.41, p = 0.01) were associated with increased risk of AS and the combined homozygous and heterozygous variant genotypes of TNF -308 G > A (rs1800629) (OR: 0.56, 95% CI: 0.44–0.72, p = 0.0002) were associated with reduced risk of AS.ConclusionWe replicated associations between AS and the polymorphisms in TNF (rs1800629), TNFRSF1A (rs4149570), and IL23R (rs11209026). Furthermore, we identified novel risk loci in TNF (rs361525), IL18 (rs187238), TLR1 (rs4833095), TLR4 (rs1554973), and LY96 (rs11465996) that need validation in independent cohorts. The results suggest that genetically determined high activity of the TNF-α, IL23/IL17, and NFkB pathways increase risk of AS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

et al. 2018

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“…To date, numerous case–control studies have been done to appraise the relationship between the TNF -308 G>A gene polymorphism and risk of leprosy susceptibility, but results from those studies yielded inconsistent and conflicting outcomes. Still, it is unclear whether this polymorphism is associated with increased or decreased susceptibility to leprosy infection [ 9 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of TNF -308 G>A (rs1800629) gene polymorphism in modulation of leprosy risk: a reappraise meta-analysis of 14 case–control studies

et al. 2017

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Purpose: Earlier studies have shown that tumor necrosis factor (TNF) -308 G>A (rs1800629) gene polymorphism is implicated in the susceptibility to leprosy, but results were inconsistent.Methods: A meta-analysis of 14 studies involving 3327 leprosy cases and 3203 controls was performed to appraise the association of TNF -308 G>A polymorphism with leprosy using MEDLINE (PUBMED), EMBASE, and Google Scholar web databases.Results: Overall, no significant association was observed in allelic (A vs. G: P=0.068; OR = 0.836, 95% CI = 0.689–1.013), homozygous (AA vs. GG: P=0.394; OR = 0.810, 95% CI = 0.499–1.315), heterozygous (GA vs. GG: P=0.059; OR = 0.780, 95% CI = 0.603–1.010), dominant (AA + GA vs. GG: P=0.067; OR = 0.797, 95% CI = 0.625–1.016), and recessive (AA vs. GG + GA: P=0.594; OR = 0.877, 95% CI = 0.542– 1.420) genetic models. Subgroup analysis showed no association in Asians. Whereas, reduced risk was found in allelic contrast (A vs. G: P=0.014; OR = 0.832, 95% CI = 0.718–0.963) and dominant models (AA + GA vs. GG: P=0.004; OR = 0.790, 95% CI = 0.673–0.928) of the mixed population.Conclusions: TNF -308 G>A polymorphism is not associated with leprosy risk in the overall population. However, subgroup analysis demonstrated protective effect of the said polymorphism in leprosy risk in the Latin American population, but showed no association in the Asians.

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The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach

Lee

Metz

McDiarmid

et al. 2021

Brain, Behavior, & Immunity - Health

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Cell culture models are valuable tools to study biological mechanisms underlying health and disease in a controlled environment. Although their genotype influences their phenotype, subtle genetic variations in cell lines are rarely characterised and taken into account for in vitro studies. To investigate how the genetic makeup of a cell line might affect the cellular response to inflammation, we characterised the single nucleotide variants (SNPs) relevant to inflammation-related genes in an established hippocampal progenitor cell line (HPC0A07/03C) that is frequently used as an in vitro model for hippocampal neurogenesis (HN). SNPs were identified using a genotyping array, and genes associated with chronic inflammatory and neuroinflammatory response gene ontology terms were retrieved using the AmiGO application. SNPs associated with these genes were then extracted from the genotyping dataset, for which a literature search was conducted, yielding relevant research articles for a total of 17 SNPs. Of these variants, 10 were found to potentially affect hippocampal neurogenesis whereby a majority (n=7) is likely to reduce neurogenesis under inflammatory conditions. Taken together, the existing literature seems to suggest that all stages of hippocampal neurogenesis could be negatively affected due to the genetic makeup in HPC0A07/03C cells under inflammation. Additional experiments will be needed to validate these specific findings in a laboratory setting. However, this computational approach already confirms that in vitro studies in general should control for cell lines subtle genetic variations which could mask or exacerbate findings.

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The − 308 bp TNF gene polymorphism influences tumor necrosis factor expression in leprosy patients in Bahia State, Brazil

Cited by 8 publications

References 34 publications

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

Impact of TNF -308 G>A (rs1800629) gene polymorphism in modulation of leprosy risk: a reappraise meta-analysis of 14 case–control studies

The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach

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The − 308 bp TNF gene polymorphism influences tumor necrosis factor expression in leprosy patients in Bahia State, Brazil

Cited by 8 publications

References 34 publications

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

Impact of TNF -308 G&gt;A (rs1800629) gene polymorphism in modulation of leprosy risk: a reappraise meta-analysis of 14 case–control studies

The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach

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Impact of TNF -308 G>A (rs1800629) gene polymorphism in modulation of leprosy risk: a reappraise meta-analysis of 14 case–control studies