Dataset Information

The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation.

ABSTRACT: In humans, allelic variants in Toll-like receptors (TLRs) associate with several pathologies. However, the underlying cellular and molecular mechanisms of this association remain largely unknown. Analysis of the human TLR9 promoter revealed that the C allele of the rs5743836 polymorphism generates several regulatory sites, including an IL-6-responding element. Here, we show that, in mononuclear cells carrying the TC genotype of rs5743836, IL-6 up-regulates TLR9 expression, leading to exacerbated cellular responses to CpG, including IL-6 production and B-cell proliferation. Our study uncovers a role for the rs5743836 polymorphism in B-cell biology with implications on TLR9-mediated diseases and on the therapeutic usage of TLR9 agonists/antagonists.

SUBMITTER: Carvalho A

PROVIDER: S-EPMC3223238 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation.

Carvalho Agostinho A Osório Nuno S NS Saraiva Margarida M Cunha Cristina C Almeida Agostinho J AJ Teixeira-Coelho Maria M Ludovico Paula P Pedrosa Jorge J Pitzurra Lucia L Aversa Franco F Romani Luigina L Castro António G AG Rodrigues Fernando F

PloS one 20111123 11

In humans, allelic variants in Toll-like receptors (TLRs) associate with several pathologies. However, the underlying cellular and molecular mechanisms of this association remain largely unknown. Analysis of the human TLR9 promoter revealed that the C allele of the rs5743836 polymorphism generates several regulatory sites, including an IL-6-responding element. Here, we show that, in mononuclear cells carrying the TC genotype of rs5743836, IL-6 up-regulates TLR9 expression, leading to exacerbated ...[more]

PMID: 22132241

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Project description:Background The relationships between the rs1801282 and rs3856806 polymorphisms in nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) gene and obesity indexes as well as serum lipid levels have been extensively investigated in various studies, but the results were inconsistent and even contradictory. Methods PubMed, Google Scholar, Embase, Cochrane Library, Web of Science, Wanfang, CNKI and VIP databases were searched for eligible studies. The random-effTPDEects model was used, and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to estimate the differences in obesity indexes and serum lipid levels between the subjects with different genotypes in a dominant model. Heterogeneity among studies was assessed by Cochran’s x2-based Q-statistic test. Publication bias was identified by using Begg’s test. Results One hundred and twenty studies (70,317 subjects) and 33 studies (18,353 subjects) were identified in the analyses for the rs1801282 and rs3856806 polymorphisms, respectively. The G allele carriers of the rs1801282 polymorphism had higher levels of body mass index (SMD = 0.08 kg/m2, 95% CI = 0.04 to 0.12 kg/m2, p < 0.001), waist circumference (SMD = 0.12 cm, 95% CI = 0.06 to 0.18 cm, p < 0.001) and total cholesterol (SMD = 0.07 mmol/L, 95% CI = 0.02 to 0.11 mmol/L, p < 0.01) than the CC homozygotes. The T allele carriers of the rs3856806 polymorphism had lower levels of low-density lipoprotein cholesterol (SMD = -0.09 mmol/L, 95% CI = -0.15 to -0.03 mmol/L, p < 0.01) and higher levels of high-density lipoprotein cholesterol (SMD = 0.06 mmol/L, 95% CI = 0.02 to 0.10 mmol/L, p < 0.01) than the CC homozygotes. Conclusions The meta-analysis suggests that the G allele of the rs1801282 polymorphism confers an increased risk of obesity and hypercholesterolemia, while the T allele of the rs3856806 polymorphism displays a protective role against dyslipidemia, which can partly explain the associations between these polymorphisms and cardiovascular disease. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier [CRD42022319347].

Dataset Information

The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation.

Publications

The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation.

Similar Datasets

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