Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis
Abstract 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 35...
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doaj-ebe017583a5d458088d5a4feb70d9e5c2020-11-25T03:53:13ZengBMCArthritis Research & Therapy1478-63622019-08-012111710.1186/s13075-019-1983-yDeletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritisKi-Nam Gu0So-Young Bang1Hye-Soon Lee2Youngho Park3Ju-Yeon Kang4Ji-Soong Kim5Bora Nam6Hyun-Seung Yoo7Jung-Min Shin8Yeon-Kyung Lee9Tae-Han Lee10Sehwan Chun11Soo-Kyung Cho12Chan-Bum Choi13Yoon-Kyoung Sung14Tae-Hwan Kim15Jae-Bum Jun16Dae Hyun Yoo17Kwangwoo Kim18Sang-Cheol Bae19Department of Biology, Kyung Hee UniversityDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Biology, Kyung Hee UniversityDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDepartment of Biology, Kyung Hee UniversityDepartment of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesAbstract 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.http://link.springer.com/article/10.1186/s13075-019-1983-yRheumatoid arthritisCopy number variationsTNF-α blockersDrug efficacy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ki-Nam Gu So-Young Bang Hye-Soon Lee Youngho Park Ju-Yeon Kang Ji-Soong Kim Bora Nam Hyun-Seung Yoo Jung-Min Shin Yeon-Kyung Lee Tae-Han Lee Sehwan Chun Soo-Kyung Cho Chan-Bum Choi Yoon-Kyoung Sung Tae-Hwan Kim Jae-Bum Jun Dae Hyun Yoo Kwangwoo Kim Sang-Cheol Bae |
spellingShingle |
Ki-Nam Gu So-Young Bang Hye-Soon Lee Youngho Park Ju-Yeon Kang Ji-Soong Kim Bora Nam Hyun-Seung Yoo Jung-Min Shin Yeon-Kyung Lee Tae-Han Lee Sehwan Chun Soo-Kyung Cho Chan-Bum Choi Yoon-Kyoung Sung Tae-Hwan Kim Jae-Bum Jun Dae Hyun Yoo Kwangwoo Kim Sang-Cheol Bae Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis Arthritis Research & Therapy Rheumatoid arthritis Copy number variations TNF-α blockers Drug efficacy |
author_facet |
Ki-Nam Gu So-Young Bang Hye-Soon Lee Youngho Park Ju-Yeon Kang Ji-Soong Kim Bora Nam Hyun-Seung Yoo Jung-Min Shin Yeon-Kyung Lee Tae-Han Lee Sehwan Chun Soo-Kyung Cho Chan-Bum Choi Yoon-Kyoung Sung Tae-Hwan Kim Jae-Bum Jun Dae Hyun Yoo Kwangwoo Kim Sang-Cheol Bae |
author_sort |
Ki-Nam Gu |
title |
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_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_sort |
deletion at 2q14.3 is associated with worse response to tnf-α blockers in patients with rheumatoid arthritis |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2019-08-01 |
description |
Abstract 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. |
topic |
Rheumatoid arthritis Copy number variations TNF-α blockers Drug efficacy |
url |
http://link.springer.com/article/10.1186/s13075-019-1983-y |
work_keys_str_mv |
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