Rheumatoid arthritis association with the FCRL3 -169C polymorphism is restricted to PTPN22 1858T-homozygous individuals in a Canadian population

William Newman, Qing Zhang, Xiangdong Liu, Erin Walker, Heather Ternan, Juile Owen, Ben Johnson, Wenda Greer, Dianne Mosher, Walter Maksymowych, Vivian Bykerk, Edward Keystone, Christopher Amos, Katherine Siminovitch

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Abstract

Objective. Variants in genes encoding the Fc receptor-like 3 (FcRL-3) and the class II major histocompatibility complex (MHC) transactivator proteins have been associated with an increased risk of rheumatoid arthritis (RA) in Japanese and Nordic populations, respectively. The aim of this study was to investigate these associations in a Canadian Caucasian cohort of RA cases and healthy controls. Methods. A total of 1,187 RA patients and 462 healthy controls were genotyped for FCRL3 and MHC2TA gene variants associated with RA. Epistasis between the FCRL3 -169C and the PTPN22 1858T variants was also examined. Results. An association was detected between RA and both the FCRL3 -169C allele (OR 1.19, P = 0.023) and the homozygous genotype (OR 1.41, P = 0.027), but association of the MHC2TA promoter region variant (-168G) with RA was not replicated. Stratification of the RA cohort by PTPN22 genotypes revealed the FCRL3 risk variant and RA association was stronger in the patient subgroup lacking PTPN22 1858T variants (P = 0.004) and was not detectable in the subgroup with PTPN22 1858T variants (P = 0.52), The PTPN22 association with RA was greater in the absence than in the presence of the FCRL3 -169C allele (P = 0.0008 versus P = 0.001). The PTPN22 1858T variant also increased the risk of autoimmune thyroid disease (AITD) in the RA patients, whereas the FCRL3 risk variant was protective against AITD. Conclusion. Our findings support an association of RA with an FCRL3 functional polymorphism and reveal that this association is stronger in the absence of PTPN22 risk genotypes. These findings support a genetic heterogeneity across RA populations, suggesting that both the FCRL3 and PTPN22 genes play roles in RA susceptibility, but in different individuals. © 2006, American College of Rheumatology
Original languageEnglish
Pages (from-to)3820-3827
Number of pages8
JournalArthritis and Rheumatology
Volume54
Issue number12
DOIs
Publication statusPublished - 2006
Externally publishedYes

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Rheumatoid Arthritis
Population
Thyroid Diseases
Genotype
Autoimmune Diseases
Alleles
Genes
Trans-Activators
Genetic Heterogeneity
Fc Receptors
Major Histocompatibility Complex
Genetic Promoter Regions

Cite this

Newman, William ; Zhang, Qing ; Liu, Xiangdong ; Walker, Erin ; Ternan, Heather ; Owen, Juile ; Johnson, Ben ; Greer, Wenda ; Mosher, Dianne ; Maksymowych, Walter ; Bykerk, Vivian ; Keystone, Edward ; Amos, Christopher ; Siminovitch, Katherine. / Rheumatoid arthritis association with the FCRL3 -169C polymorphism is restricted to PTPN22 1858T-homozygous individuals in a Canadian population. In: Arthritis and Rheumatology. 2006 ; Vol. 54, No. 12. pp. 3820-3827.
@article{8628207f220946adabd5ea928c72e26d,
title = "Rheumatoid arthritis association with the FCRL3 -169C polymorphism is restricted to PTPN22 1858T-homozygous individuals in a Canadian population",
abstract = "Objective. Variants in genes encoding the Fc receptor-like 3 (FcRL-3) and the class II major histocompatibility complex (MHC) transactivator proteins have been associated with an increased risk of rheumatoid arthritis (RA) in Japanese and Nordic populations, respectively. The aim of this study was to investigate these associations in a Canadian Caucasian cohort of RA cases and healthy controls. Methods. A total of 1,187 RA patients and 462 healthy controls were genotyped for FCRL3 and MHC2TA gene variants associated with RA. Epistasis between the FCRL3 -169C and the PTPN22 1858T variants was also examined. Results. An association was detected between RA and both the FCRL3 -169C allele (OR 1.19, P = 0.023) and the homozygous genotype (OR 1.41, P = 0.027), but association of the MHC2TA promoter region variant (-168G) with RA was not replicated. Stratification of the RA cohort by PTPN22 genotypes revealed the FCRL3 risk variant and RA association was stronger in the patient subgroup lacking PTPN22 1858T variants (P = 0.004) and was not detectable in the subgroup with PTPN22 1858T variants (P = 0.52), The PTPN22 association with RA was greater in the absence than in the presence of the FCRL3 -169C allele (P = 0.0008 versus P = 0.001). The PTPN22 1858T variant also increased the risk of autoimmune thyroid disease (AITD) in the RA patients, whereas the FCRL3 risk variant was protective against AITD. Conclusion. Our findings support an association of RA with an FCRL3 functional polymorphism and reveal that this association is stronger in the absence of PTPN22 risk genotypes. These findings support a genetic heterogeneity across RA populations, suggesting that both the FCRL3 and PTPN22 genes play roles in RA susceptibility, but in different individuals. {\circledC} 2006, American College of Rheumatology",
author = "William Newman and Qing Zhang and Xiangdong Liu and Erin Walker and Heather Ternan and Juile Owen and Ben Johnson and Wenda Greer and Dianne Mosher and Walter Maksymowych and Vivian Bykerk and Edward Keystone and Christopher Amos and Katherine Siminovitch",
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doi = "10.1002/art.22270",
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Newman, W, Zhang, Q, Liu, X, Walker, E, Ternan, H, Owen, J, Johnson, B, Greer, W, Mosher, D, Maksymowych, W, Bykerk, V, Keystone, E, Amos, C & Siminovitch, K 2006, 'Rheumatoid arthritis association with the FCRL3 -169C polymorphism is restricted to PTPN22 1858T-homozygous individuals in a Canadian population', Arthritis and Rheumatology, vol. 54, no. 12, pp. 3820-3827. https://doi.org/10.1002/art.22270

Rheumatoid arthritis association with the FCRL3 -169C polymorphism is restricted to PTPN22 1858T-homozygous individuals in a Canadian population. / Newman, William; Zhang, Qing; Liu, Xiangdong; Walker, Erin; Ternan, Heather; Owen, Juile; Johnson, Ben; Greer, Wenda; Mosher, Dianne; Maksymowych, Walter; Bykerk, Vivian; Keystone, Edward; Amos, Christopher; Siminovitch, Katherine.

In: Arthritis and Rheumatology, Vol. 54, No. 12, 2006, p. 3820-3827.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rheumatoid arthritis association with the FCRL3 -169C polymorphism is restricted to PTPN22 1858T-homozygous individuals in a Canadian population

AU - Newman, William

AU - Zhang, Qing

AU - Liu, Xiangdong

AU - Walker, Erin

AU - Ternan, Heather

AU - Owen, Juile

AU - Johnson, Ben

AU - Greer, Wenda

AU - Mosher, Dianne

AU - Maksymowych, Walter

AU - Bykerk, Vivian

AU - Keystone, Edward

AU - Amos, Christopher

AU - Siminovitch, Katherine

PY - 2006

Y1 - 2006

N2 - Objective. Variants in genes encoding the Fc receptor-like 3 (FcRL-3) and the class II major histocompatibility complex (MHC) transactivator proteins have been associated with an increased risk of rheumatoid arthritis (RA) in Japanese and Nordic populations, respectively. The aim of this study was to investigate these associations in a Canadian Caucasian cohort of RA cases and healthy controls. Methods. A total of 1,187 RA patients and 462 healthy controls were genotyped for FCRL3 and MHC2TA gene variants associated with RA. Epistasis between the FCRL3 -169C and the PTPN22 1858T variants was also examined. Results. An association was detected between RA and both the FCRL3 -169C allele (OR 1.19, P = 0.023) and the homozygous genotype (OR 1.41, P = 0.027), but association of the MHC2TA promoter region variant (-168G) with RA was not replicated. Stratification of the RA cohort by PTPN22 genotypes revealed the FCRL3 risk variant and RA association was stronger in the patient subgroup lacking PTPN22 1858T variants (P = 0.004) and was not detectable in the subgroup with PTPN22 1858T variants (P = 0.52), The PTPN22 association with RA was greater in the absence than in the presence of the FCRL3 -169C allele (P = 0.0008 versus P = 0.001). The PTPN22 1858T variant also increased the risk of autoimmune thyroid disease (AITD) in the RA patients, whereas the FCRL3 risk variant was protective against AITD. Conclusion. Our findings support an association of RA with an FCRL3 functional polymorphism and reveal that this association is stronger in the absence of PTPN22 risk genotypes. These findings support a genetic heterogeneity across RA populations, suggesting that both the FCRL3 and PTPN22 genes play roles in RA susceptibility, but in different individuals. © 2006, American College of Rheumatology

AB - Objective. Variants in genes encoding the Fc receptor-like 3 (FcRL-3) and the class II major histocompatibility complex (MHC) transactivator proteins have been associated with an increased risk of rheumatoid arthritis (RA) in Japanese and Nordic populations, respectively. The aim of this study was to investigate these associations in a Canadian Caucasian cohort of RA cases and healthy controls. Methods. A total of 1,187 RA patients and 462 healthy controls were genotyped for FCRL3 and MHC2TA gene variants associated with RA. Epistasis between the FCRL3 -169C and the PTPN22 1858T variants was also examined. Results. An association was detected between RA and both the FCRL3 -169C allele (OR 1.19, P = 0.023) and the homozygous genotype (OR 1.41, P = 0.027), but association of the MHC2TA promoter region variant (-168G) with RA was not replicated. Stratification of the RA cohort by PTPN22 genotypes revealed the FCRL3 risk variant and RA association was stronger in the patient subgroup lacking PTPN22 1858T variants (P = 0.004) and was not detectable in the subgroup with PTPN22 1858T variants (P = 0.52), The PTPN22 association with RA was greater in the absence than in the presence of the FCRL3 -169C allele (P = 0.0008 versus P = 0.001). The PTPN22 1858T variant also increased the risk of autoimmune thyroid disease (AITD) in the RA patients, whereas the FCRL3 risk variant was protective against AITD. Conclusion. Our findings support an association of RA with an FCRL3 functional polymorphism and reveal that this association is stronger in the absence of PTPN22 risk genotypes. These findings support a genetic heterogeneity across RA populations, suggesting that both the FCRL3 and PTPN22 genes play roles in RA susceptibility, but in different individuals. © 2006, American College of Rheumatology

U2 - 10.1002/art.22270

DO - 10.1002/art.22270

M3 - Article

VL - 54

SP - 3820

EP - 3827

JO - Arthritis Rheumatism

JF - Arthritis Rheumatism

SN - 0004-3591

IS - 12

ER -