Dataset Information

Deletion at 2q14.3 is associated with worse response to TNF-? 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-? blockers.

Methods

A total of 357 Korean patients with RA were examined for the efficacy of TNF-? 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-? blockers was analyzed by multivariate logistic regression accounting for genetic background and clinical factors including body mass index, gender, baseline disease activity, TNF-? blocker used, and methotrexate treatment.

Results

The study subjects varied in their responses to TNF-? 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-? 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-? 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-? blockers.

SUBMITTER: Gu KN

PROVIDER: S-EPMC6714408 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis.

Gu Ki-Nam KN Bang So-Young SY Lee Hye-Soon HS Park Youngho Y Kang Ju-Yeon JY Kim Ji-Soong JS Nam Bora B Yoo Hyun-Seung HS Shin Jung-Min JM Lee Yeon-Kyung YK Lee Tae-Han TH Chun Sehwan S Cho Soo-Kyung SK Choi Chan-Bum CB Sung Yoon-Kyoung YK Kim Tae-Hwan TH Jun Jae-Bum JB Yoo Dae Hyun DH Kim Kwangwoo K Bae Sang-Cheol SC

Arthritis research & therapy 20190828 1

<h4>Background</h4>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.<h4>Methods</h4>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 classi ...[more]

PMID: 31462329

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