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Michael Chen-Xu,
Ruth Topless,
Cushla McKinney,
Marilyn E Merriman, Amanda Phipps-Green,
Nicola Dalbeth,
Peter J Gow,
Andrew A Harrison,
John Highton,
Peter B Jones, [......],
Dora Pascual-Salcedo,
Ana M Ortiz,
Miguel A Gonzalez-Gay,
Sophia Steer,
Marthe Maehlen,
Benedicte Lie,
B Paul Wordsworth,
Lisa K Stamp,
Javier Martin,
Tony R Merriman
Annals of the rheumatic diseases 09/2011; 71(1):155-7. · 8.11 Impact Factor
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Amanda Phipps-Green,
Cushla McKinney,
Manuela Rossol,
Marilyn E Merriman,
Ruth Topless,
Jade E Hollis-Moffatt,
Wan Rohani Wan Taib,
Nicola Dalbeth,
Peter J Gow,
Andrew A Harrison,
John Highton,
Peter B B Jones,
Lisa K Stamp,
Ulf Wanger,
Paul Wordsworth,
Tony R Merriman
Annals of the rheumatic diseases 02/2011; 70(8):1512-4. · 8.11 Impact Factor
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Cushla McKinney,
Manuela Fanciulli,
Marilyn E Merriman, Amanda Phipps-Green,
Behrooz Z Alizadeh,
Bobby P C Koeleman,
Nicola Dalbeth,
Peter J Gow,
Andrew A Harrison,
John Highton, [......],
Lisa K Stamp,
Sophia Steer,
Pilar Barrera,
Marieke J H Coenen,
Barbara Franke,
Piet L C M van Riel,
Tim J Vyse,
Tim J Aitman,
Timothy R D J Radstake,
Tony R Merriman
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ABSTRACT: There is increasing evidence that variation in gene copy number (CN) influences clinical phenotype. The low-affinity Fcgamma receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment to sites of inflammation and activation of polymorphonuclear neutrophils (PMNs). Given recent evidence that low FCGR3B CN is a risk factor for systemic but not organ-specific autoimmune disease and the potential importance of PMN in the pathophysiology of rheumatoid arthritis (RA), the authors hypothesised that FCGR3B gene dosage influences susceptibility to RA.
FCGR3B CN was measured in 643 cases of RA and 461 controls from New Zealand (NZ), with follow-up analysis in 768 cases and 702 controls from the Netherlands and 250 cases and 211 controls from the UK. All subjects were of Caucasian ancestry.
Significant evidence for an association between CN <2 and RA was observed in the Dutch cohort (OR 2.01 (95% CI 1.37 to 2.94), p=3 x 10-4) but not in the two smaller cohorts (OR 1.45 (95% CI 0.92 to 2.26), p=0.11 and OR 1.33 (95% CI 0.58 to 3.02), p=0.50 for the NZ and UK populations, respectively). The association was evident in a meta-analysis which included a previously published Caucasian sample set (OR 1.67 (95% CI 1.28 to 2.17), p=1.2 x 10-4).
One possible mechanism to explain the association between reduced FCGR3B CN and RA is the reduced clearance of immune complex during inflammation. However, it is not known whether the association between RA and FCGR3B CN is aetiological or acts as a proxy marker for another biologically relevant variant. More detailed examination of genetic variation within the FCGR gene cluster is required.
Annals of the rheumatic diseases 09/2010; 69(9):1711-6. · 8.11 Impact Factor
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Jade E Hollis-Moffatt,
Kerry A Rowley, Amanda J Phipps-Green,
Marilyn E Merriman,
Nicola Dalbeth,
Peter Gow,
Andrew A Harrison,
John Highton,
Peter B B Jones,
Lisa K Stamp,
Pille Harrison,
B Paul Wordsworth,
Tony R Merriman
[show abstract]
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ABSTRACT: Angiogenesis is an important process in the development of destructive synovial pannus in rheumatoid arthritis (RA). The ITGAV +gene encodes a cell cycle-associated antigen, integrin alphanubeta 3, which plays a role in RA angiogenesis. Previously, two independent studies identified an association between the major allele of the ITGAV single-nucleotide polymorphism (SNP) rs3738919 and RA. We therefore tested this association in an independent study using New Zealand (NZ) and Oxford (UK) RA case control samples.
We compared genotype frequencies in 740 NZ Caucasian RA patients and 553 controls genotyped for rs3738919, using a polymerase chain reaction-restriction fragment length polymorphism assay. A TaqMan genotyping SNP assay was used to type 713 Caucasian RA patients and 515 control samples from Oxford for the rs3738919 variant. Association of rs3738919 with RA was tested in these two sample sets using the chi-square goodness-of-fit test. The Mantel-Haenszel test was used to perform a meta-analysis, combining the genetic results from four independent Caucasian case control cohorts, consisting of 3,527 cases and 4,126 controls. Haplotype analysis was also performed using SNPs rs3911238, rs10174098 and rs3738919 in the Wellcome Trust Case Control Consortium, NZ and Oxford case control samples.
We found no evidence for association between ITGAV and RA in either the NZ or Oxford sample set (odds ratio [OR] = 0.88, P(allelic) = 0.11 and OR = 1.18, P(allelic) = 0.07, respectively). Inclusion of these data in a meta-analysis (random effects) of four independent cohorts (3,527 cases and 4,126 controls) weakens support for the hypothesis that rs3738919 plays a role in the development of RA (OR(combined) = 0.92, 95% confidence interval 0.80 to 1.07; P = 0.29). No consistent haplotype associations were evident.
Association of ITGAV SNP rs7378919 with RA was not replicated in NZ or Oxford case control sample sets. Meta-analysis of these and previously published data lends limited support for a role for the ITGAV in RA in Caucasians of European ancestry.
Arthritis research & therapy 10/2009; 11(5):R152. · 4.27 Impact Factor
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[show abstract]
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ABSTRACT: Sustained-release formulations have drawn the attention of formulation scientists working in the area of vaccine research because these systems may reduce the need for booster immunisations. This would be of great advantage especially for the administration of subunit vaccines. The aim of this study was to illustrate the performance of liposome-forming, sustained-release lipid implants containing 2% of the adjuvant Quil-A (QA) (w/w of total lipids) and ovalbumin (OVA) as a model antigen, in an in vivo study using C57Bl/6 mice. QA/OVA-containing lipid implants were administered subcutaneously and stimulated a similar magnitude of immune response when compared with an immediate-release formulation that contained an equivalent amount of adjuvant and antigen but was administered twice. The novel implant system presented here combines the advantages of both sustained release and particulate delivery in one formulation.
Journal of Drug Targeting 05/2008; 16(3):224-32. · 2.70 Impact Factor
