Combining effects of polymorphism of tumor necrosis factor α 5′-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis

Ichikawa, Naomi; Kotake, Shigeru; Hakoda, Masayuki; Higami, Kenshi; Kawasaki, Aya; Furuya, Takefumi; Nanke, Yuki; Tsuchiya, Naoyuki; Tokunaga, Katsushi; Kamatani, Naoyuki

doi:10.1007/s10165-008-0134-0

Cited by 3 publications

(3 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNF-α -863A polymorphism has been reported to be associated with RA susceptibility in Japanese [123,124], Turkish [126], and Thai populations [125]. The frequency of TNF -863A allele in Japanese patients with systemic JRA was significantly higher than those in controls.…”

Section: Tnf-α -863 Polymorphisms and Susceptibility To Ramentioning

confidence: 92%

The role of TNF-α and TNF-β gene polymorphism in the pathogenesis of Rheumatoid Arthritis

Rayes

Arfin

Tariq

et al. 2013

RHC

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder of unknown etiology that affects the synovial membrane of multiple joints. The clinical presentation of RA may vary from mild to severe with excessive erosions of periarticular bone leading to the loss of functional capacity. Both genetic and environmental factors are important in the development of this disorder. The genetic contribution to susceptibility for RA is underlined by a three-to four-fold higher concordance percentage for clinically expressed disease in monozygotic twins compared to dizygotic twins. The severity and long term outcome of RA have also been related to various genetic factors. Tumor necrosis factor (TNF), a pro-inflammatory cytokine, is involved in the pathogenesis of a variety of autoimmune disorders, including RA. A large number of studies have been undertaken to determine the role of TNF-α promoter polymorphisms in the pathogenesis of RA. On the other hand few attempts have been made to identify the association between TNF-α (lymphotoxin-alfa) polymorphism and RA. In this narrative review of published literature, an attempt has been made to determine the association between TNF-α promoter polymorphisms at positions –308, –238, –489, –857, –863 and TNF-β at +252 with respect to susceptibility to and severity of RA, as well as response to drug therapy. In spite of intra-and inter-ethnic variations, analysis of data suggests a significant role of TNF-α/TNF-β polymorphisms in determining the susceptibility/severity of RA and responsiveness to anti-TNF drug therapy. The TNF gene polymorphisms may be an interesting target for novel strategies to prevent RA and/or in its early treatment. Further studies using larger samples are needed to pinpoint the regulatory polymorphisms or haplotypes and their effects on the development of certain manifestations in RA.

show abstract

Section: Tnf-α -863 Polymorphisms and Susceptibility To Ramentioning

confidence: 92%

The role of TNF-α and TNF-β gene polymorphism in the pathogenesis of Rheumatoid Arthritis

Rayes

Arfin

Tariq

et al. 2013

RHC

View full text Add to dashboard Cite

show abstract

“…However, these risk alleles differ among ethnic populations. HLA-DRB1 *0401, 0404 and *0101 are the most common RA risk alleles among those of European ancestry (30, 31), while HLA-DRB1 *0405 is the most common RA susceptibility allele for East Asian populations (32, 33). PTPN22 rs2476601 is a susceptibility locus for people of European ancestry, but is not associated with RA in Asian populations (6, 34, 35).…”

Section: Data Collection and Database Contentmentioning

confidence: 99%

RADB: a database of rheumatoid arthritis-related polymorphisms

et al. 2014

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune disease that has a complex genetic basis. Therefore, it is important to explore the genetic background of RA. The extensive recent application of polymorphic genetic markers, especially single nucleotide polymorphisms, has presented us with a large quantity of genetic data. In this study, we developed the Database of Rheumatoid Arthritis-related Polymorphisms (RADB), to integrate all the RA-related genetic polymorphisms and provide a useful resource for researchers. We manually extracted the RA-related polymorphisms from 686 published reports, including RA susceptibility loci, polymorphisms associated with particular clinical features of RA, polymorphisms associated with drug response in RA and polymorphisms associated with a higher risk of cardiovascular disease in RA. Currently, RADB V1.0 contains 3235 polymorphisms that are associated with 636 genes and refer to 68 countries. The detailed information extracted from the literature includes basic information about the articles (e.g. PubMed ID, title and abstract), population information (e.g. country, geographic area and sample size) and polymorphism information (e.g. polymorphism name, gene, genotype, odds ratio and 95% confidence interval, P-value and risk allele). Meanwhile, useful annotations, such as hyperlinks to dbSNP, GenBank, UCSC, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway, are included. In addition, a tool for meta-analysis was developed to summarize the results of multiple studies. The database is freely available at http://www.bioapp.org/RADB.Database URL: http://www.bioapp.org/RADB.

show abstract

“…For this we selected reported markers/genes from inflammatory pathway and a few oxidative stress pathway genes involved in inflammation. Inflammatory pathway genes were selected as most of the candidate gene studies [11] , [12] , [13] , [14] and GWAS have implicated a role of these genes in RA [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] . Oxidative stress pathway was selected based on evidence of association of genes like SOD3, PON1 and PON2 with joint diseases/RA [25] , [26] , [27] , [28] and their commonly implicated polymorphisms with inflammatory conditions [29] , [30] , [31] , [32] .…”

Section: Introductionmentioning

confidence: 99%

Potential of Ayurgenomics Approach in Complex Trait Research: Leads from a Pilot Study on Rheumatoid Arthritis

et al. 2012

View full text Add to dashboard Cite

BackgroundInconsistent results across association studies including Genome-wide association, have posed a major challenge in complex disease genetics. Of the several factors which contribute to this, phenotypic heterogeneity is a serious limitation encountered in modern medicine. On the other hand, Ayurveda, a holistic Indian traditional system of medicine, enables subgrouping of individuals into three major categories namely Vata, Pitta and Kapha, based on their physical and mental constitution, referred to as Prakriti. We hypothesised that conditioning association studies on prior risk, predictable in Ayurveda, will uncover much more variance and potentially open up more predictive health.Objectives and MethodsIdentification of genetic susceptibility markers by combining the prakriti based subgrouping of individuals with genetic analysis tools was attempted in a Rheumatoid arthritis (RA) cohort. Association of 21 markers from commonly implicated inflammatory and oxidative stress pathways was tested using a case-control approach in a total cohort comprising 325 cases and 356 controls and in the three subgroups separately. We also tested few postulates of Ayurveda on the disease characteristics in different prakriti groups using clinico-genetic data.ResultsInflammatory genes like IL1β (C-C-C haplotype, p = 0.0005, OR = 3.09) and CD40 (rs4810485 allelic, p = 0.04, OR = 2.27) seem to be the determinants in Vata subgroup whereas oxidative stress pathway genes are observed in Pitta (SOD3 rs699473, p = 0.004, OR = 1.83; rs2536512 p = 0.005; OR = 1.88 and PON1 rs662, p = 0.04, OR = 1.53) and Kapha (SOD3 rs2536512, genotypic, p = 0.02, OR = 2.39) subgroups. Fixed effect analysis of the associated markers from CD40, SOD3 and TNFα with genotype X prakriti interaction terms suggests heterogeneity of effects within the subgroups. Further, disease characteristics such as severity was most pronounced in Vata group.ConclusionsThis exploratory study suggests discrete causal pathways for RA etiology in prakriti based subgroups, thereby, validating concepts of prakriti and personalized medicine in Ayurveda. Ayurgenomics approach holds promise for biomarker discovery in complex diseases.

show abstract

Combining effects of polymorphism of tumor necrosis factor α 5′-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis

Cited by 3 publications

References 18 publications

The role of TNF-α and TNF-β gene polymorphism in the pathogenesis of Rheumatoid Arthritis

The role of TNF-α and TNF-β gene polymorphism in the pathogenesis of Rheumatoid Arthritis

RADB: a database of rheumatoid arthritis-related polymorphisms

Potential of Ayurgenomics Approach in Complex Trait Research: Leads from a Pilot Study on Rheumatoid Arthritis

Contact Info

Product

Resources

About