Oncotarget

Research Papers:

rs2841277 (PLD4) is associated with susceptibility and rs4672495 is associated with disease activity in rheumatoid arthritis

Wei-Chiao Chen, Wen-Chang Wang, Hsing-Fang Lu, Yukinori Okada, Wei-Pin Chang, Yii-Her Chou, Hui-Hua Chang, Jin-Ding Huang, Der-Yuan Chen _ and Wei-Chiao Chang

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Oncotarget. 2017; 8:64180-64190. https://doi.org/10.18632/oncotarget.19419

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Abstract

Wei-Chiao Chen1,*, Wen-Chang Wang2,3,* Hsing-Fang Lu4, Yukinori Okada5, Wei-Pin Chang6, Yii-Her Chou7,8, Hui-Hua Chang1,9, Jin-Ding Huang1, Der-Yuan Chen10,11,12,13 and Wei-Chiao Chang2,3,4,14,15

1Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

2The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

3Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan

4Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan

5Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan

6School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan

7Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

8Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

9School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan

10Department of Internal Medicine and Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan

11Faculty of Medicine, National Yang Ming University, Taipei, Taiwan

12Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan

13Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan

14Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan

15Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Der-Yuan Chen, email: dychen@vghtc.gov.tw

Wei-Chiao Chang, email: wcc@tmu.edu.tw

Keywords: rheumatoid arthritis (RA), phospholipase D family, member 4 (PLD4), rs2841277, rs4672495

Received: May 01, 2017     Accepted: June 05, 2017     Published: July 18, 2017

ABSTRACT

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, can lead to long-term joint damage, chronic pain, and loss of motor function in the hands, and may share some common genetic factors with other autoimmune disorders, such as ankylosing spondylitis (AS). Many single-nucleotide polymorphisms (SNPs) were reported by genome-wide association studies (GWASs) of RA, but some of them have not been examined in the Taiwanese population. In this study, for 15 SNPs reported in previous RA and AS GWASs, we investigated their association with RA in a Taiwanese population. Based on 334 RA patients recruited from the Taichung Veterans General Hospital and 16,036 healthy subjects from the Taiwan Biobank (TWB) project, we observed that subjects having minor allele C at rs2841277 (phospholipase D family, member 4 (PLD4)) have lower susceptibility of RA, compare to those having genotype TT (Odds ratio (OR) = 0.6, p = 3.0 x 10-6). Among the RA patients, we observed that subjects having GG at rs4672495 have a lower proportion of severe RA, compare to other subjects (OR = 0.09, p = 5.6 x 10-3). Results of a bioinformatics approach showed that rs2841277 is able to influence expression of LINC00638 and AHNAK2 and rs4672495 is able to influence the expression of B3GNT2. In summary, this study replicated an association of rs2841277 with RA susceptibility and showed an AS-associated SNP, rs4672495, is associated with RA activity in the Taiwanese population.


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