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Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis
BACKGROUND: Structural variations such as copy number variations (CNVs) have a functional impact on various human traits. This study profiled genome-wide CNVs in Korean patients with rheumatoid arthritis (RA) to investigate the efficacy of treatment with TNF-α blockers. METHODS: A total of 357 Korea...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714408/ https://www.ncbi.nlm.nih.gov/pubmed/31462329 http://dx.doi.org/10.1186/s13075-019-1983-y |
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author | Gu, Ki-Nam Bang, So-Young Lee, Hye-Soon Park, Youngho Kang, Ju-Yeon Kim, Ji-Soong Nam, Bora Yoo, Hyun-Seung Shin, Jung-Min Lee, Yeon-Kyung Lee, Tae-Han Chun, Sehwan Cho, Soo-Kyung Choi, Chan-Bum Sung, Yoon-Kyoung Kim, Tae-Hwan Jun, Jae-Bum Yoo, Dae Hyun Kim, Kwangwoo Bae, Sang-Cheol |
author_facet | Gu, Ki-Nam Bang, So-Young Lee, Hye-Soon Park, Youngho Kang, Ju-Yeon Kim, Ji-Soong Nam, Bora Yoo, Hyun-Seung Shin, Jung-Min Lee, Yeon-Kyung Lee, Tae-Han Chun, Sehwan Cho, Soo-Kyung Choi, Chan-Bum Sung, Yoon-Kyoung Kim, Tae-Hwan Jun, Jae-Bum Yoo, Dae Hyun Kim, Kwangwoo Bae, Sang-Cheol |
author_sort | Gu, Ki-Nam |
collection | PubMed |
description | BACKGROUND: Structural variations such as copy number variations (CNVs) have a functional impact on various human traits. This study profiled genome-wide CNVs in Korean patients with rheumatoid arthritis (RA) to investigate the efficacy of treatment with TNF-α blockers. METHODS: A total of 357 Korean patients with RA were examined for the efficacy of TNF-α blocker treatment. Disease activity indexes were measured at baseline and 6 months after the treatment. The patients were classified as responders and non-responders based on the change in disease activity indexes according to the EULAR response criteria. CNVs in the same patients were profiled using fluorescence signal intensity data generated by a genome-wide SNP array. The association of CNVs with response to TNF-α blockers was analyzed by multivariate logistic regression accounting for genetic background and clinical factors including body mass index, gender, baseline disease activity, TNF-α blocker used, and methotrexate treatment. RESULTS: The study subjects varied in their responses to TNF-α blockers and had 286 common CNVs in autosomes. We identified that the 3.8-kb deletion at 2q14.3 in 5% of the subjects was associated with response to TNF-α blockers (1.37 × 10(− 5) ≤ P ≤ 4.07 × 10(− 4)) at a false discovery rate threshold of 5%. The deletion in the identified CNV was significantly more frequent in the non-responders than in the responders, indicating worse response to TNF-α blockers in the deletion carriers. The 3.8-kb deletion at 2q14.3 is located in an intergenic region with the binding sites of two transcription factors, MAFF and MAFK. CONCLUSIONS: This study obtained the CNV landscape of Korean patients with RA and identified the common regional deletion associated with poor response to treatment with TNF-α blockers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1983-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6714408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67144082019-09-04 Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis Gu, Ki-Nam Bang, So-Young Lee, Hye-Soon Park, Youngho Kang, Ju-Yeon Kim, Ji-Soong Nam, Bora Yoo, Hyun-Seung Shin, Jung-Min Lee, Yeon-Kyung Lee, Tae-Han Chun, Sehwan Cho, Soo-Kyung Choi, Chan-Bum Sung, Yoon-Kyoung Kim, Tae-Hwan Jun, Jae-Bum Yoo, Dae Hyun Kim, Kwangwoo Bae, Sang-Cheol Arthritis Res Ther Research Article BACKGROUND: Structural variations such as copy number variations (CNVs) have a functional impact on various human traits. This study profiled genome-wide CNVs in Korean patients with rheumatoid arthritis (RA) to investigate the efficacy of treatment with TNF-α blockers. METHODS: A total of 357 Korean patients with RA were examined for the efficacy of TNF-α blocker treatment. Disease activity indexes were measured at baseline and 6 months after the treatment. The patients were classified as responders and non-responders based on the change in disease activity indexes according to the EULAR response criteria. CNVs in the same patients were profiled using fluorescence signal intensity data generated by a genome-wide SNP array. The association of CNVs with response to TNF-α blockers was analyzed by multivariate logistic regression accounting for genetic background and clinical factors including body mass index, gender, baseline disease activity, TNF-α blocker used, and methotrexate treatment. RESULTS: The study subjects varied in their responses to TNF-α blockers and had 286 common CNVs in autosomes. We identified that the 3.8-kb deletion at 2q14.3 in 5% of the subjects was associated with response to TNF-α blockers (1.37 × 10(− 5) ≤ P ≤ 4.07 × 10(− 4)) at a false discovery rate threshold of 5%. The deletion in the identified CNV was significantly more frequent in the non-responders than in the responders, indicating worse response to TNF-α blockers in the deletion carriers. The 3.8-kb deletion at 2q14.3 is located in an intergenic region with the binding sites of two transcription factors, MAFF and MAFK. CONCLUSIONS: This study obtained the CNV landscape of Korean patients with RA and identified the common regional deletion associated with poor response to treatment with TNF-α blockers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1983-y) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-28 2019 /pmc/articles/PMC6714408/ /pubmed/31462329 http://dx.doi.org/10.1186/s13075-019-1983-y Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Gu, Ki-Nam Bang, So-Young Lee, Hye-Soon Park, Youngho Kang, Ju-Yeon Kim, Ji-Soong Nam, Bora Yoo, Hyun-Seung Shin, Jung-Min Lee, Yeon-Kyung Lee, Tae-Han Chun, Sehwan Cho, Soo-Kyung Choi, Chan-Bum Sung, Yoon-Kyoung Kim, Tae-Hwan Jun, Jae-Bum Yoo, Dae Hyun Kim, Kwangwoo Bae, Sang-Cheol Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis |
title | Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis |
title_full | Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis |
title_fullStr | Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis |
title_full_unstemmed | Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis |
title_short | Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis |
title_sort | deletion at 2q14.3 is associated with worse response to tnf-α blockers in patients with rheumatoid arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714408/ https://www.ncbi.nlm.nih.gov/pubmed/31462329 http://dx.doi.org/10.1186/s13075-019-1983-y |
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