Int J Med Sci 2019; 16(10):1397-1403. doi:10.7150/ijms.34659

Research Paper

VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis

Chengqian Dai1*, Shu-Jui Kuo2,3*, Sung-Lin Hu2,4, Chun-Hao Tsai2,3, Yuan-Li Huang5, Chien-Chung Huang2,6, Lihong Wang1, Guohong Xu1, Chen-Ming Su7✉, Chih-Hsin Tang2,5,8✉

1. Department of Orthopedics, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
2. School of Medicine, China Medical University, Taichung, Taiwan
3. Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
4. Department of Family Medicine, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
5. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
6. Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
7. Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
8. Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
*Equally contributed as first authors

Abstract

Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; p = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; p = 0.01). Our findings suggest that VEGF-C gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the VEGF-C gene may be promising for RA treatment.

Keywords: single nucleotide polymorphism, rheumatoid arthritis, VEGF-C

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How to cite this article:
Dai C, Kuo SJ, Hu SL, Tsai CH, Huang YL, Huang CC, Wang L, Xu G, Su CM, Tang CH. VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis. Int J Med Sci 2019; 16(10):1397-1403. doi:10.7150/ijms.34659. Available from http://www.medsci.org/v16p1397.htm