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A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus

OBJECTIVE: Thrombosis is a serious complication of systemic lupus erythematosus (SLE). Studies that have investigated the genetics of thrombosis in SLE are limited. We undertook this study to assess the association of previously implicated candidate genes, particularly Toll-like receptor (TLR) genes...

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Autores principales: Kaiser, Rachel, Tang, Ling Fung, Taylor, Kimberly E, Sterba, Kirsten, Nititham, Joanne, Brown, Elizabeth E, Edberg, Jeffrey C, McGwin, Gerald, Alarcón, Graciela S, Ramsey-Goldman, Rosalind, Reveille, John D, Vilá, Luis M, Petri, Michelle, Rauch, Joyce, Miller, Emily, Mesznik, Kara, Kwok, Pui-Yan, Kimberly, Robert P, Salmon, Jane E, Criswell, Lindsey A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269184/
https://www.ncbi.nlm.nih.gov/pubmed/24578102
http://dx.doi.org/10.1002/art.38520
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author Kaiser, Rachel
Tang, Ling Fung
Taylor, Kimberly E
Sterba, Kirsten
Nititham, Joanne
Brown, Elizabeth E
Edberg, Jeffrey C
McGwin, Gerald
Alarcón, Graciela S
Ramsey-Goldman, Rosalind
Reveille, John D
Vilá, Luis M
Petri, Michelle
Rauch, Joyce
Miller, Emily
Mesznik, Kara
Kwok, Pui-Yan
Kimberly, Robert P
Salmon, Jane E
Criswell, Lindsey A
author_facet Kaiser, Rachel
Tang, Ling Fung
Taylor, Kimberly E
Sterba, Kirsten
Nititham, Joanne
Brown, Elizabeth E
Edberg, Jeffrey C
McGwin, Gerald
Alarcón, Graciela S
Ramsey-Goldman, Rosalind
Reveille, John D
Vilá, Luis M
Petri, Michelle
Rauch, Joyce
Miller, Emily
Mesznik, Kara
Kwok, Pui-Yan
Kimberly, Robert P
Salmon, Jane E
Criswell, Lindsey A
author_sort Kaiser, Rachel
collection PubMed
description OBJECTIVE: Thrombosis is a serious complication of systemic lupus erythematosus (SLE). Studies that have investigated the genetics of thrombosis in SLE are limited. We undertook this study to assess the association of previously implicated candidate genes, particularly Toll-like receptor (TLR) genes, with pathogenesis of thrombosis. METHODS: We genotyped 3,587 SLE patients from 3 multiethnic populations for 77 single-nucleotide polymorphisms (SNPs) in 10 genes, primarily in TLRs 2, 4, 7, and 9, and we also genotyped 64 ancestry-informative markers (AIMs). We first analyzed association with arterial and venous thrombosis in the combined population via logistic regression, adjusting for top principal components of the AIMs and other covariates. We also subjected an associated SNP, rs893629, to meta-analysis (after stratification by ethnicity and study population) to confirm the association and to test for study population or ethnicity effects. RESULTS: In the combined analysis, the SNP rs893629 in the KIAA0922/TLR2 region was significantly associated with arterial thrombosis (logistic P = 6.4 × 10(−5), false discovery rate P = 0.0044). Two additional SNPs in TLR2 were also suggestive: rs1816702 (logistic P = 0.002) and rs4235232 (logistic P = 0.009). In the meta-analysis by study population, the odds ratio (OR) for arterial thrombosis with rs893629 was 2.44 (95% confidence interval 1.58–3.76), without evidence for heterogeneity (P = 0.78). By ethnicity, the effect was most significant among African Americans (OR 2.42, P = 3.5 × 10(−4)) and European Americans (OR 3.47, P = 0.024). CONCLUSION: TLR2 gene variation is associated with thrombosis in SLE, particularly among African Americans and European Americans. There was no evidence of association among Hispanics, and results in Asian Americans were limited due to insufficient sample size. These results may help elucidate the pathogenesis of this important clinical manifestation.
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spelling pubmed-42691842014-12-22 A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus Kaiser, Rachel Tang, Ling Fung Taylor, Kimberly E Sterba, Kirsten Nititham, Joanne Brown, Elizabeth E Edberg, Jeffrey C McGwin, Gerald Alarcón, Graciela S Ramsey-Goldman, Rosalind Reveille, John D Vilá, Luis M Petri, Michelle Rauch, Joyce Miller, Emily Mesznik, Kara Kwok, Pui-Yan Kimberly, Robert P Salmon, Jane E Criswell, Lindsey A Arthritis Rheumatol Brief Report OBJECTIVE: Thrombosis is a serious complication of systemic lupus erythematosus (SLE). Studies that have investigated the genetics of thrombosis in SLE are limited. We undertook this study to assess the association of previously implicated candidate genes, particularly Toll-like receptor (TLR) genes, with pathogenesis of thrombosis. METHODS: We genotyped 3,587 SLE patients from 3 multiethnic populations for 77 single-nucleotide polymorphisms (SNPs) in 10 genes, primarily in TLRs 2, 4, 7, and 9, and we also genotyped 64 ancestry-informative markers (AIMs). We first analyzed association with arterial and venous thrombosis in the combined population via logistic regression, adjusting for top principal components of the AIMs and other covariates. We also subjected an associated SNP, rs893629, to meta-analysis (after stratification by ethnicity and study population) to confirm the association and to test for study population or ethnicity effects. RESULTS: In the combined analysis, the SNP rs893629 in the KIAA0922/TLR2 region was significantly associated with arterial thrombosis (logistic P = 6.4 × 10(−5), false discovery rate P = 0.0044). Two additional SNPs in TLR2 were also suggestive: rs1816702 (logistic P = 0.002) and rs4235232 (logistic P = 0.009). In the meta-analysis by study population, the odds ratio (OR) for arterial thrombosis with rs893629 was 2.44 (95% confidence interval 1.58–3.76), without evidence for heterogeneity (P = 0.78). By ethnicity, the effect was most significant among African Americans (OR 2.42, P = 3.5 × 10(−4)) and European Americans (OR 3.47, P = 0.024). CONCLUSION: TLR2 gene variation is associated with thrombosis in SLE, particularly among African Americans and European Americans. There was no evidence of association among Hispanics, and results in Asian Americans were limited due to insufficient sample size. These results may help elucidate the pathogenesis of this important clinical manifestation. BlackWell Publishing Ltd 2014-07 2014-06-27 /pmc/articles/PMC4269184/ /pubmed/24578102 http://dx.doi.org/10.1002/art.38520 Text en © 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Brief Report
Kaiser, Rachel
Tang, Ling Fung
Taylor, Kimberly E
Sterba, Kirsten
Nititham, Joanne
Brown, Elizabeth E
Edberg, Jeffrey C
McGwin, Gerald
Alarcón, Graciela S
Ramsey-Goldman, Rosalind
Reveille, John D
Vilá, Luis M
Petri, Michelle
Rauch, Joyce
Miller, Emily
Mesznik, Kara
Kwok, Pui-Yan
Kimberly, Robert P
Salmon, Jane E
Criswell, Lindsey A
A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus
title A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus
title_full A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus
title_fullStr A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus
title_full_unstemmed A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus
title_short A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus
title_sort polymorphism in tlr2 is associated with arterial thrombosis in a multiethnic population of patients with systemic lupus erythematosus
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269184/
https://www.ncbi.nlm.nih.gov/pubmed/24578102
http://dx.doi.org/10.1002/art.38520
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