Novel genetic association of the<i>VTCN1</i>region with rheumatoid arthritis

Daha, Nina A.; Lie, Benedicte A.; Trouw, Leendert A.; Stoeken, G.; Schonkeren, Joris; Ding, Bo; Kvien, Tore K; Schilham, Marco W.; Padyukov, Leonid; Huizinga, T.W.J.; Toes, René E. M.

doi:10.1136/annrheumdis-2011-200574

Cited by 14 publications

(10 citation statements)

References 18 publications

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“…VTCN1 rs10923223 polymorphism has also been associated with disease course in JIA [53]. In support of a critical role for this gene in inflammatory arthritis, variants in VTCN1 were found to be associated with RA in a Dutch cohort [55]. …”

Section: Genetics Of Oligoarticular Jia/polyarticular Rf-negative Jiamentioning

confidence: 99%

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Hersh

Prahalad

2015

Journal of Autoimmunity

118

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Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a complex genetic trait influenced by both genetic and environmental factors. Twin and family studies suggest a substantial role for genetic factors in the predisposition to JIA. Describing the genetics is complicated by the heterogeneity of JIA; the International League of Associations for Rheumatology (ILAR) has defined seven categories of JIA based on distinct clinical and laboratory features. Utilizing a variety of techniques including candidate gene studies, the use of genotyping arrays such as Immunochip, and genome wide association studies (GWAS), both human leukocyte antigen (HLA) and non-HLA susceptibility loci associated with JIA have been described. Several of these polymorphisms (e.g. HLA class II, PTPN22, STAT4) are shared with other common autoimmune conditions; other novel polymorphisms that have been identified may be unique to JIA. Associations with oligoarticular and RF-negative polyarticular JIA are the best characterized. A strong association between HLA DRB1:11:03/04 and DRB1:08:01, and a protective effect of DRB1:15:01 have been described. HLA DPB1:02:01 has also been associated with oligoarticular and RF-negative polyarticular JIA. Besides PTPN22, STAT4 and PTPN2 variants, IL2, IL2RA, IL2RB, as well as IL6 and IL6R loci also harbor variants associated with oligoarticular and RF-negative polyarticular JIA. RF-positive polyarticular JIA is associated with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22, STAT4 and TNFAIP3 variants. ERA is associated with HLA B27. Most other associations between JIA categories and HLA or non-HLA variants need confirmation. The formation of International Consortia to ascertain and analyze large cohorts of JIA categories, validation of reported findings in independent cohorts, and functional studies will enhance our understanding of the genetic underpinnings of JIA.

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Section: Genetics Of Oligoarticular Jia/polyarticular Rf-negative Jiamentioning

confidence: 99%

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Hersh

Prahalad

2015

Journal of Autoimmunity

118

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“…Outside the MHC, several suggestive associations in ACPAÀ disease have been reported [26][27][28], and a genome-wide significant association has been found at the locus including ANKRD55 GWAS results have highlighted regulatory T cells and CD4 þ memory T cells as critical cell types in RA.…”

Section: Rheumatoid Arthritis Risk Loci Outside the Mhcmentioning

confidence: 99%

Genome-wide association studies to advance our understanding of critical cell types and pathways in rheumatoid arthritis

Diogo

Okada

Plenge

2014

Current Opinion in Rheumatology

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“…The GWAS failed to identify specific susceptibility loci to ACPA-negative RA beyond the GWAS significance level. Several studies from mainly European countries using candidate gene approach have reported susceptibility markers to ACPA-negative RA [ 26 - 30 ], but none of them were specific to ACPA-negative RA with strong P -values, due to their limited numbers of subjects.…”

Section: Introductionmentioning

confidence: 99%

Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population

et al. 2015

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IntroductionAlthough susceptibility genes for anti-citrullinated peptide/protein antibodies (ACPA)-positive rheumatoid arthritis (RA) have been successfully discovered by genome-wide association studies (GWAS), little is known about the genetic background of ACPA-negative RA. We intended to elucidate genetic background of ACPA-negative RA.MethodWe performed a meta-analysis of GWAS comprising 670 ACPA-negative RA and 16,891 controls for 1,948,138 markers, followed by a replication study of the top 35 single nucleotide polymorphisms (SNPs) using 916 cases and 3,764 controls. Inverse-variance method was applied to assess overall effects. To assess overlap of susceptibility loci between ACPA-positive and -negative RA, odds ratios (ORs) of the 21 susceptibility markers to RA in Japanese were compared between the two subsets. In addition, SNPs were stratified by the p-values in GWAS meta-analysis for either ACPA-positive RA or ACPA-negative RA to address the question whether weakly-associated genes were also shared. The correlations between ACPA-positive RA and the subpopulations of ACPA-negative RA (rheumatoid factor (RF)-positive and RF-negative subsets) were also addressed.ResultsRs6904716 in LEMD2 of the human leukocyte antigen (HLA) locus showed a borderline association with ACPA-negative RA (overall p = 5.7 × 10−8), followed by rs6986423 in CSMD1 (p = 2.4 × 10−6) and rs17727339 in FCRL3 (p = 1.4 × 10−5). ACPA-negative RA showed significant correlations of ORs with ACPA-positive RA for the 21 susceptibility SNPs and non-HLA SNPs with p-values far from significance. These significant correlations with ACPA-positive RA were true for ACPA-negative RF-positive and ACPA-negative RF-negative RA. On the contrary, positive correlations were not observed between the ACPA-negative two subpopulations.ConclusionMany of the susceptibility loci were shared between ACPA-positive and -negative RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0623-4) contains supplementary material, which is available to authorized users.

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Novel genetic association of theVTCN1region with rheumatoid arthritis

Abstract: These results indicate a novel genetic association with the VTCN1 region in RA susceptibility.

Cited by 14 publications

References 18 publications

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Genome-wide association studies to advance our understanding of critical cell types and pathways in rheumatoid arthritis

Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population

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