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Significant association between TAP2 polymorphisms and rheumatoid arthritis: a meta-analysis.

ABSTRACT: Rheumatoid arthritis (RA) is a severe chronic immune mediated inflammatory disease that has been shown to be associated with human leukocyte antigen (HLA) loci. The transporter associated with antigen processing 2 (TAP2) has been identified to play an important role in the HLA-associated diseases and immune response. The goal of our meta-analysis was to summarize the contribution of TAP2 polymorphisms to the risk of RA.Meta-analyses were performed between RA and 3 TAP2 coding polymorphisms that comprised TAP2-379Ile?>?Val (rs1800454), TAP2-565Ala?>?Thr (rs2228396) and TAP2-665Thr?>?Ala (rs241447). The meta-analyses were involved with 9 studies (24 individual studies) among 973 cases and 965 controls.Meta-analyses showed that TAP2-379Ile allele was significantly associated with an increased risk of RA (p?=?0.0002, odds ratio (OR)?=?1.44, 95% confidence interval (CI)?=?1.18-1.74). This association was further shown only in the dominant model (p?=?0.006, OR?=?1.59, 95% CI?=?1.14-2.22). Subgroup analyses by ethnicity revealed that the association of TAP2-379Ile was significant in Asians (p?=?0.03, OR?=?1.38, 95% CI?=?1.04-1.83). In addition, another significant association of TAP2-565Thr allele with RA was observed in Europeans (p?=?0.002, OR?=?1.62, 95% CI?=?1.20-2.20).Our meta-analyses suggested that TAP2-379Ile allele was significantly associated with a 59% increased risk in the dominant effect model. Subgroup analyses by ethnicity showed that TAP2-379-Ile increased the risk of RA by 38% in Asians and TAP2-565Thr increased the risk of RA by 38% in Europeans.The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2097080313124700.

SUBMITTER: Dai D

PROVIDER: S-EPMC4090395 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Significant association between TAP2 polymorphisms and rheumatoid arthritis: a meta-analysis.

Dai Dongjun D Chen Yong Y Ru Ping P Zhou Xingyu X Tao Jianmin J Ye Huadan H Hong Qingxiao Q Tang Linlin L Pan Guanghui G Lin Danfeng D Gong Qiongyao Q Lv Yuelong Y Xu Leiting L Duan Shiwei S

Diagnostic pathology 20140627

<h4>Background</h4>Rheumatoid arthritis (RA) is a severe chronic immune mediated inflammatory disease that has been shown to be associated with human leukocyte antigen (HLA) loci. The transporter associated with antigen processing 2 (TAP2) has been identified to play an important role in the HLA-associated diseases and immune response. The goal of our meta-analysis was to summarize the contribution of TAP2 polymorphisms to the risk of RA.<h4>Methods</h4>Meta-analyses were performed between RA an ...[more]

PMID: 24972609

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Project description:Rheumatoid arthritis (RA) is the most common systemic inflammatory disease and is of unknown etiology. The altered balance between immunosuppressive and inflammatory T cell subpopulations exerts a huge impact on RA pathogenesis. The STAT3 protein regulates genes involved in the immune responses. It regulates maturation of T and B cells. Its abnormal activity is significantly associated with autoimmune diseases and cancer development. We aimed to evaluate the contribution of three potentially functional single nucleotide polymorphisms (SNPs) within the STAT3 gene to susceptibility and severity of RA in the Polish population.A total of 595 patients with RA and 330 healthy individuals were included in the study. DNA from patients and healthy subjects was obtained from peripheral blood using standard DNA isolating methods. The STAT3 rs1053005, rs1026916 and rs2293152 polymorphisms were genotyped using the TaqMan SNP genotyping assay. The accuracy of SNP genotyping was confirmed using direct DNA sequence analysis.The distribution of STAT3 polymorphisms did not differ significantly between cases and controls. Our results revealed a tendency only, where rs1026916 AA genotype occurred more frequently in RA patients compared to healthy controls, in codominant (p = 0.09), dominant (p = 0.06) and recessive (p = 0.09) models. STAT3 rs2293152 polymorphism was associated with higher DAS28 (p = 0.014 codominant model; p = 0.003 dominant model), increased number of swollen joints (p = 0.02), higher VAS (p = 0.01) and higher HAQ score (p = 0.05).We did not observe a significant association between the three studied STAT3 genetic variants and increased susceptibility to or severity of RA. Only the STAT3 rs2293152 polymorphism was associated with parameters that indicate a more severe course of the disease. However, its distribution did not differ between RA and control groups. According to our observations these 3 studied STAT3 SNPs may not be used as risk factors for developing RA.

Project description:BackgroundUltrasonography (US) can directly demonstrate joint inflammation, including grayscale (GS) signs of synovial hypertrophy and power Doppler (PD) techniques to demonstrate increased blood flow and vascularization. Recently, echogenicity, especially hypoechoic synovium, has also been associated with local inflammatory activity. However, only a few studies have demonstrated correlation between histopathologic and immunopathologic evaluation and US findings. The aim of this study was to clarify whether joint US findings including synovial hypertrophy, vascularity, and echogenicity can accurately characterize synovial pathophysiology in patients with active rheumatoid arthritis (RA).MethodsA total of 44 patients with RA were included, both treated (n?=?25) and untreated (n?=?19) and scheduled for US examination of the knee joint with synovial fluid (SF) aspiration and two treated patients also underwent synovial biopsy. US images were quantitatively analyzed using grayscale assessment of synovial hypertrophy and PD for vascularity and echogenicity. Levels of nine SF cytokines and growth factors were also measured.ResultsBoth US synovial hypertrophy and PD vascularity significantly correlated with SF inflammatory cytokine levels such as IL-6, IL-8, IL-1? and IL-10 in untreated patients. Angiogenic factors, including vascular endothelial growth factor (VEGF), only correlated with PD vascularity. In the treated patients, the associations between synovial hypertrophy and any cytokines were diminished, although synovial vascularity and echogenicity correlated with IL-6 and VEGF (p?<?0.05). Histopathologic analysis revealed that hypoechogenicity of the synovium correlated with marked infiltration of lymphocytes and hypervascularity.ConclusionsWe demonstrated the pathophysiological origins of US findings in the joint. The degree of US vascularity of the synovium correlated with local inflammatory cytokine levels and angiogenetic factors in patients with active RA. Synovial echogenicity, and not hypertrophy, correlated with inflammation, especially in treated patients with RA.

Project description:Aims: Rheumatoid arthritis (RA) is characterized by cartilage and bone damage leading to disability. Here, the association between microRNA (miRNA) polymorphisms and susceptibility to RA was evaluated by performing an updated meta-analysis and systematic review. Main methods: An electronic search of databases including PubMed and Embase was performed from inception to December 8, 2017 to retrieve studies investigating the association between miRNA polymorphisms and RA risk. Two reviewers independently screened literature according to the inclusion and exclusion criteria and extracted data. The meta-analysis was conducted using Stata 14.0 software. Key findings: Thirteen case-control studies with 2660 cases and 4098 controls were screened out after a systematic search. One study from the miR-146a rs2910164 G > C polymorphism group and two from the miR-499 rs3746444 T > C polymorphism group were excluded because of deviations from Hardy-Weinberg equilibrium. Pooled analysis demonstrated that miR-146a rs2910164 G > C polymorphism was not significantly associated with susceptibility to RA. However, a significant association was observed between miR-499 rs3746444 T > C polymorphism and RA risk (C vs. T: OR = 1.22, 95% CI = 1.05-1.42, P = 0.008; TC vs. TT: OR = 1.26, 95% CI = 1.05-1.50, P = 0.011; TC/CC vs. TT: OR = 1.26, 95% CI = 1.07-1.5, P = 0.007). Subgroup analysis based on ethnicity showed no significant association between miR-499 T > C polymorphism and susceptibility to RA in the Asian population (P > 0.05). However, in Caucasian population, the C allele in the miR-499 T > C polymorphism was a contributor to RA susceptibility in some genetic models (C vs. T: OR = 1.64, 95% CI = 1.28-2.11, P < 0.001; TC vs. TT: OR = 1.95, 95% CI = 1.40-2.71, P < 0.001; TC/CC vs. TT: OR = 1.96, 95% CI = 1.43-2.69, P < 0.001). Significance: The miR-146a rs2910164 G > C polymorphism was not associated with susceptibility to RA. In the Caucasian population, the C allele in the miR-499 T > C polymorphism contributed to RA susceptibility.

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Significant association between TAP2 polymorphisms and rheumatoid arthritis: a meta-analysis.

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Significant association between TAP2 polymorphisms and rheumatoid arthritis: a meta-analysis.

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