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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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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. |
format | Online Article Text |
id | pubmed-4269184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
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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