Associations Between Genetic Polymorphisms Within Transporter Genes and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients: A Pilot Study

Han Cen; Qin-Wen Wen; Han-Qing Zhang; Hang Yu; Zhen Zeng; Ting Jin; Ting-Hui Wang; Wen Qin; Hua Huang; Xiu-Di Wu

doi:10.2147/PGPM.S350417

Associations Between Genetic Polymorphisms Within Transporter Genes and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients: A Pilot Study

Pharmgenomics Pers Med. 2022 Apr 12:15:327-339. doi: 10.2147/PGPM.S350417. eCollection 2022.

Authors

Han Cen^{1

2

3}, Qin-Wen Wen⁴, Han-Qing Zhang⁴, Hang Yu⁴, Zhen Zeng², Ting Jin², Ting-Hui Wang⁴, Wen Qin⁴, Hua Huang⁴, Xiu-Di Wu⁴

Affiliations

¹ Institute of Geriatrics, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People's Republic of China.
² Department of Preventive Medicine, Medical School of Ningbo University, Ningbo, Zhejiang, People's Republic of China.
³ Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, People's Republic of China.
⁴ Department of Rheumatology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang, People's Republic of China.

Abstract

Purpose: To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients.

Patients and methods: A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR >0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1~4 and ABCG2, were genotyped.

Results: Multivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR >0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CCC.

Conclusion: Our results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.

Keywords: clinical response; methotrexate; rheumatoid arthritis; single-nucleotide polymorphism; transporter.