The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp.
The Trp(620) allotype of PTPN22 confers susceptibility to rheumatoid arthritis (RA) and certain other classical autoimmune diseases. There has been a report of other variants within the PTPN22 locus that alter risk of RA; protective haplotype '5', haplotype group '6-10' and susce...
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doaj-ca5ae3831f32472aac787e787a72fd652020-11-24T20:47:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-10-01510e1354410.1371/journal.pone.0013544The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp.Wan R Wan TaibDeborah J SmythMarilyn E MerrimanNicola DalbethPeter J GowAndrew A HarrisonJohn HightonPeter B B JonesLisa StampSophia SteerJohn A ToddTony R MerrimanThe Trp(620) allotype of PTPN22 confers susceptibility to rheumatoid arthritis (RA) and certain other classical autoimmune diseases. There has been a report of other variants within the PTPN22 locus that alter risk of RA; protective haplotype '5', haplotype group '6-10' and susceptibility haplotype '4', suggesting the possibility of other PTPN22 variants involved in the pathogenesis of RA independent of R620W (rs2476601). Our aim was to further investigate this possibility.A total of 4,460 RA cases and 4,481 controls, all European, were analysed. Single nucleotide polymorphisms rs3789607, rs12144309, rs3811021 and rs12566340 were genotyped over New Zealand (NZ) and UK samples. Publically-available Wellcome Trust Case Control Consortium (WTCCC) genotype data were used.The protective effect of haplotype 5 was confirmed (rs3789607; (OR = 0.91, P = 0.016), and a second protective effect (possibly of haplotype 6) was observed (rs12144309; OR = 0.90, P = 0.021). The previously reported susceptibility effect of haplotype 4 was not replicated; instead a protective effect was observed (rs3811021; OR = 0.85, P = 1.4×10(-5)). Haplotypes defined by rs3789607, rs12144309 and rs3811021 coalesced with the major allele of rs12566340 within the adjacent BFK (B-cell lymphoma 2 (BCL2) family kin) gene. We, therefore, tested rs12566340 for association with RA conditional on rs2476601; there was no evidence for an independent effect at rs12566340 (P = 0.76). Similarly, there was no evidence for an independent effect at rs12566340 in type 1 diabetes (P = 0.85).We have no evidence for a common variant additional to rs2476601 within the PTPN22 locus that influences the risk of RA. Arg620Trp is almost certainly the single common causal variant.http://europepmc.org/articles/PMC2958827?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wan R Wan Taib Deborah J Smyth Marilyn E Merriman Nicola Dalbeth Peter J Gow Andrew A Harrison John Highton Peter B B Jones Lisa Stamp Sophia Steer John A Todd Tony R Merriman |
spellingShingle |
Wan R Wan Taib Deborah J Smyth Marilyn E Merriman Nicola Dalbeth Peter J Gow Andrew A Harrison John Highton Peter B B Jones Lisa Stamp Sophia Steer John A Todd Tony R Merriman The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp. PLoS ONE |
author_facet |
Wan R Wan Taib Deborah J Smyth Marilyn E Merriman Nicola Dalbeth Peter J Gow Andrew A Harrison John Highton Peter B B Jones Lisa Stamp Sophia Steer John A Todd Tony R Merriman |
author_sort |
Wan R Wan Taib |
title |
The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp. |
title_short |
The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp. |
title_full |
The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp. |
title_fullStr |
The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp. |
title_full_unstemmed |
The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp. |
title_sort |
ptpn22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of arg620trp. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2010-10-01 |
description |
The Trp(620) allotype of PTPN22 confers susceptibility to rheumatoid arthritis (RA) and certain other classical autoimmune diseases. There has been a report of other variants within the PTPN22 locus that alter risk of RA; protective haplotype '5', haplotype group '6-10' and susceptibility haplotype '4', suggesting the possibility of other PTPN22 variants involved in the pathogenesis of RA independent of R620W (rs2476601). Our aim was to further investigate this possibility.A total of 4,460 RA cases and 4,481 controls, all European, were analysed. Single nucleotide polymorphisms rs3789607, rs12144309, rs3811021 and rs12566340 were genotyped over New Zealand (NZ) and UK samples. Publically-available Wellcome Trust Case Control Consortium (WTCCC) genotype data were used.The protective effect of haplotype 5 was confirmed (rs3789607; (OR = 0.91, P = 0.016), and a second protective effect (possibly of haplotype 6) was observed (rs12144309; OR = 0.90, P = 0.021). The previously reported susceptibility effect of haplotype 4 was not replicated; instead a protective effect was observed (rs3811021; OR = 0.85, P = 1.4×10(-5)). Haplotypes defined by rs3789607, rs12144309 and rs3811021 coalesced with the major allele of rs12566340 within the adjacent BFK (B-cell lymphoma 2 (BCL2) family kin) gene. We, therefore, tested rs12566340 for association with RA conditional on rs2476601; there was no evidence for an independent effect at rs12566340 (P = 0.76). Similarly, there was no evidence for an independent effect at rs12566340 in type 1 diabetes (P = 0.85).We have no evidence for a common variant additional to rs2476601 within the PTPN22 locus that influences the risk of RA. Arg620Trp is almost certainly the single common causal variant. |
url |
http://europepmc.org/articles/PMC2958827?pdf=render |
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