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

Wei-Chiao Chen; Wen-Chang Wang; Yukinori Okada; Wei-Pin Chang; Yii-Her Chou; Hui-Hua Chang; Jin-Ding Huang; Der-Yuan Chen; Wei-Chiao Chang

doi:10.18632/oncotarget.19419

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

Oncotarget. 2017 Jul 18;8(38):64180-64190. doi: 10.18632/oncotarget.19419. eCollection 2017 Sep 8.

Authors

Wei-Chiao Chen^#¹, Wen-Chang Wang^#², Yukinori Okada³, Wei-Pin Chang⁴, Yii-Her Chou^{5

6}, Hui-Hua Chang^{1

7}, Jin-Ding Huang¹, Der-Yuan Chen^{8

9

10

11}, Wei-Chiao Chang^{2

12

13

14

15}

Affiliations

¹ Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
³ Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁴ School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁶ Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁸ Department of Internal Medicine and Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan.
⁹ Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.
¹⁰ Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
¹¹ Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
¹² Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
¹³ Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
¹⁴ Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁵ Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.

^# Contributed equally.

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 × 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 × 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.

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