A Barton

A Hinks

E Flynn

J Cobb

J Packham

J Worthington

null null

P Martin

S Eyre

W Thomson

English

PubMed

Springer - Publisher Connector

Replication of the association of the COG6 gene with juvenile idiopathic arthritis (JIA)

POSTER PRESENTATION Open Access
Replication of the association of the COG6 gene
with juvenile idiopathic arthritis (JIA)
A Hinks1*, J Cobb1, P Martin1, E Flynn1, S Eyre1, J Packham2, Childhood Arthritis Prospective Study (CAPS),
BSPAR study group, A Barton1, J Worthington1, W Thomson1
From 18th Pediatric Rheumatology European Society (PReS) Congress
Bruges, Belgium. 14-18 September 2011
Background
A large US JIA case control study investigating SNPs
previously implicated in autoimmune diseases recently
identified three novel JIA loci, protein tyrosine phos-
phatase, non-receptor type 2 (PTPN2), conserved oli-
gomeric golgi complex component 6 (COG6) and
angiopoietin 1 (ANGPT1). We have previously shown
association of SNPs in the PTPN2 gene in our UK JIA
cohort.
Aim
To test whether the two additional loci also confer sus-
ceptibility to JIA in a UK cohort.
Methods
Two SNPs, rs7993214, near the COG6 gene and
rs1010824, near the ANGPT1 gene, were genotyped in
UK JIA cases (n=817) and the genotype and allele fre-
quency data compared with those for healthy controls
(n=5196) extracted from the Wellcome Trust case
control consortium 2 (WTCCC2) European Genome-
phenome Archive (EGA). The Cochrane-Armitage trend
test implemented in PLINK was performed and allelic
odds ratios (ORs) and their 95% confidence intervals
(CIs) calculated.
Results
This study had >90% power to detect an effect equiva-
lent to that identified for these loci in the original study.
No association was found for the SNP in ANGPT1
(ptrend = 0.85). The SNP near the COG6 gene,
rs7993214, was significantly associated with JIA overall
(ptrend = 0.03 OR 0.9 95% CI 0.81-0.99). Analysis of
only the oligoarthritis and RF negative polyarthritis sub-
types, the subtypes investigated in the US study,
revealed a trend towards association (ptrend = 0.06 OR
0.9 95% CI 0.8-1.01). Our study suggests however that
this SNP maybe associated in other JIA subtypes, indeed
despite comparatively small numbers (n=123) the asso-
ciation was also significant in the systemic onset subtype
(p=0.03). Meta-analysis of this study with the original
study provided genome wide significant association of
this SNP with JIA (combined p-value=8.5 x 10-7 OR
0.84 95% CI 0.78-0.9) with no evidence of heterogeneity
between the two studies.
Conclusions
We present replication of the association of a SNP near
the COG6 gene and JIA. Meta-analysis of this study with
the original US study provided genome wide significance
for this locus in oligoarticular JIA and RF negative polyar-
thritis JIA. The SNP lies within an intergenic region
between the COG6 and FOXO1 genes. COG6 is a compo-
nent of the conserved oligomeric golgi complex, which
plays a role in glycoprotein modification and intracellular
transport. FOXO1 belongs to the forkhead family of tran-
scription factors and may be important in regulatory
T cell development and function. Further genetic analysis
will be required to identify the causal SNP and gene
important in JIA susceptibility.
Author details
1Arthritis Research UK Epidemiology Unit, Manchester Academic Health
Science Centre (MAHSC), Stopford Building, University of Manchester,
Manchester, UK. 2Haywood Hospital, University Hospital of North
Staffordshire, Stoke on Trent, Staffordshire, UK.
* Correspondence: Anne.Hinks@manchester.ac.uk
1Arthritis Research UK Epidemiology Unit, Manchester Academic Health
Science Centre (MAHSC), Stopford Building, University of Manchester,
Manchester, UK
Full list of author information is available at the end of the article
Hinks et al. Pediatric Rheumatology 2011, 9(Suppl 1):P281
http://www.ped-rheum.com/content/9/S1/P281
© 2011 Hinks et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Published: 14 September 2011
doi:10.1186/1546-0096-9-S1-P281
Cite this article as: Hinks et al.: Replication of the association of the
COG6 gene with juvenile idiopathic arthritis (JIA). Pediatric Rheumatology
2011 9(Suppl 1):P281.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Hinks et al. Pediatric Rheumatology 2011, 9(Suppl 1):P281
http://www.ped-rheum.com/content/9/S1/P281
Page 2 of 2


Crossref

Pediatric Rheumatology

Worthington J

Barton A

Packham J

Eyre S

Flynn E

Martin P

Cobb J

Hinks A

Thomson W

Directory of Open Access Journals

Replication of the association of the <it>COG6</it> gene with juvenile idiopathic arthritis (JIA)

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3194648

Replication of the association of the COG6 gene with juvenile idiopathic arthritis (JIA)

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

Springer - Publisher Connector

Crossref

Directory of Open Access Journals