Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis

Barton, Anne; Eyre, Steve; Symmons, Deborah; Worthington, Jane; Silman, Alan J.

doi:10.1136/ard.2004.034173

Cited by 32 publications

(26 citation statements)

References 15 publications

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“…Disease severity can differ considerably between cohorts. When the polymorphism of a target gene is related to disease severity rather than susceptibility, the false-positive results in association studies could be caused by selection bias of recruiting patients with more severe disease [44]. The present study links SNPs of the FCRL3 gene with disease severity, implying that the conflicting results of previous genetic association studies of FCRL3 SNPs might have resulted, at least partially, from the difference in disease severity of RA between study populations.…”

Section: Figcontrasting

confidence: 44%

FCRL3 gene polymorphisms contribute to the radiographic severity rather than susceptibility of rheumatoid arthritis

Han¹,

Hee²,

Kim³

et al. 2012

Human Immunology

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Section: Figcontrasting

confidence: 44%

FCRL3 gene polymorphisms contribute to the radiographic severity rather than susceptibility of rheumatoid arthritis

Han¹,

Hee²,

Kim³

et al. 2012

Human Immunology

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“…Although this study focused on East Asian populations, it is important to ascertain whether PADI4 SNPs confer RA risk in a race-specific manner. In white populations, previous association studies have produced inconsistent results (Barton et al 2005a;Harney et al 2005;Martinez et al 2005;Plenge et al 2005;Hoppe et al 2006). However, recent ethnicity-specific meta-analyses have suggested that the padi4_94 SNP may be associated with increased risk of RA in Europeans, although the magnitude of association seemed to be much smaller than that in Asians, and further analysis with a much larger sample size is therefore needed to draw a conclusion (Iwamoto et al 2006;Lee et al 2007).…”

Section: Discussionmentioning

confidence: 92%

“…Further analyses revealed the susceptible haplotype marked by disease-associated SNPs to be functional, affecting the stability of PADI4 mRNA, and its frequency was associated with the development of anti-CCP antibody-positive RA. The genetic association between PADI4 and RA was replicated in another Japanese group ) and in a Korean population , although many studies of Caucasian subjects yielded conflicting findings (Barton et al 2005a;Harney et al 2005;Martinez et al 2005;Plenge et al 2005;Hoppe et al 2006). Recent meta-analyses of PADI4 SNPs, however, hinted at an association in European RA patients (Iwamoto et al 2006;Lee et al 2007).…”

Section: Introductionmentioning

confidence: 98%

Replication of reported genetic associations of PADI4, FCRL3, SLC22A4 and RUNX1 genes with rheumatoid arthritis: results of an independent Japanese population and evidence from meta-analysis of East Asian studies

et al. 2007

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We conducted population-based association tests for the four selected SNPs (rs2240340/padi4_94, rs7528684/fcrl3_3, rs3792876/slc2F2 and rs2268277/ runx1) previously reported to be associated with rheumatoid arthritis (RA). The study population consisted of 950 unrelated Japanese subjects with RA and 507 controls, none of whom had previously been tested for these variants. Only the SNP rs2240340/padi4_94 was modestly associated with RA [allele odds ratio (OR) 1.22, 95% confidence interval (CI) 1.04-1.43, P = 0.012]. The most significant association effect was found for genotype contrast between minor and major allele homozygotes (OR 1.53, 95% CI 1.10-2.12, P = 0.010). No other SNPs showed a statistically significant association with RA in our population. Meta-analysis of published studies and our new data confirmed a highly significant association between PADI4 gene SNPs and increased risk of RA in East Asian populations (allele fixed-effects summary OR 1.31, 95% CI 1.22-1.41, P \ 0.0001). We found some evidence for an association of either rs7528684/fcrl3_3 or rs3792876/slc2F2 with RA; however, because the magnitudes of effects were apparently much weaker than those reported in the initial positive reports, and there were substantial levels of inter-study OR heterogeneity, we concluded that additional studies are needed to fully understand the present results.

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“…Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease of unknown aetiology where combinations of genetic and environmental factors have been shown to be relevant contributory factors to the expression and complications of the disease [1][2][3][4][5][6]. A number of genes (HLA-DRB1, TRAF1/C5, STAT4, REL, PTPN22, TNF , IL2/ IL21, CTLA4, TNFRII, VDR, etc.)…”

Section: Introductionmentioning

confidence: 99%

Association analysis of TNFR2, VDR, A2M, GSTT1, GSTM1, and ACE genes with rheumatoid arthritis in South Asians and Caucasians of East Midlands in the United Kingdom

et al. 2010

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Genetic associations of TNFR2, VDR (Bsm I and Fok I), A2M, GSTT(1), GSTM(1) and ACE in South Asian and Caucasian patients with rheumatoid arthritis (RA) were assessed in this study. DNA samples from South Asians (134 cases, 149 controls) and Caucasians (137 cases, 150 controls) from the East Midlands of the United Kingdom were genotyped for seven polymorphisms. All cases were rheumatoid-factor positive. Significant genetic associations were observed with TNFR2 R-R (OR = 3.16, CI 1.20-9.26, P < 0.05), A2M 1-1 (OR = 2.09, CI 1.21-3.64, P < 0.05) and GST T(1)null (OR = 1.97, CI 1.07-3.68, P < 0.05) among Caucasian patients. In South Asians, VDR Bsm I B-B genotype (OR = 2.08, CI 1.23-3.52, P < 0.05), A2M 2-2 genotype (OR = 3.99, CI 1.19-17.18, P < 0.05), and GST T(1)null genotype (OR = 2.81, CI 1.40-5.77, P < 0.002) genotypes were associated with RA. In the majority of cases, recessive and multiplicative modes of inheritance explained the observed associations. This study demonstrates that ethnicity affects the genetic associations in RA.

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Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis

Cited by 32 publications

References 15 publications

FCRL3 gene polymorphisms contribute to the radiographic severity rather than susceptibility of rheumatoid arthritis

FCRL3 gene polymorphisms contribute to the radiographic severity rather than susceptibility of rheumatoid arthritis

Replication of reported genetic associations of PADI4, FCRL3, SLC22A4 and RUNX1 genes with rheumatoid arthritis: results of an independent Japanese population and evidence from meta-analysis of East Asian studies

Association analysis of TNFR2, VDR, A2M, GSTT1, GSTM1, and ACE genes with rheumatoid arthritis in South Asians and Caucasians of East Midlands in the United Kingdom

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