MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis

Qian Zhang,1,2 Pan Fu,2 Zhanglei Cao,2 Hua Huang,3 Qinwen Wen,3 Kaizhe Wang,2 Tong Kong,2 Xiudi Wu,3 Jianping Zheng2 1Jiangxi Key Laboratory for Rare Earths Magnetic Materials and Devices, College of Rare Earths, Jiangxi University of Science and Technology, Ganzhou, 341000, People’s Republic of Chi...

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Main Authors: Zhang Q, Fu P, Cao Z, Huang H, Wen Q, Wang K, Kong T, Wu X, Zheng J
Format: Article
Language:English
Published: Dove Medical Press 2023-05-01
Series:Pharmacogenomics and Personalized Medicine
Subjects:
Online Access:https://www.dovepress.com/mthfr-and-mtrr-genetic-polymorphism-of-methotrexate-therapy-outcomes-i-peer-reviewed-fulltext-article-PGPM
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author Zhang Q
Fu P
Cao Z
Huang H
Wen Q
Wang K
Kong T
Wu X
Zheng J
author_facet Zhang Q
Fu P
Cao Z
Huang H
Wen Q
Wang K
Kong T
Wu X
Zheng J
author_sort Zhang Q
collection DOAJ
description Qian Zhang,1,2 Pan Fu,2 Zhanglei Cao,2 Hua Huang,3 Qinwen Wen,3 Kaizhe Wang,2 Tong Kong,2 Xiudi Wu,3 Jianping Zheng2 1Jiangxi Key Laboratory for Rare Earths Magnetic Materials and Devices, College of Rare Earths, Jiangxi University of Science and Technology, Ganzhou, 341000, People’s Republic of China; 2Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences (CAS), Ningbo, 315300, People’s Republic of China; 3Department of Rheumatology and Immunology, Ningbo First Hospital, Ningbo, 315010, People’s Republic of ChinaCorrespondence: Jianping Zheng; Xiudi Wu, Tel +86– 18091984088 ; +86– 13857826442, Email zhengjianping@nimte.ac.cn; awu1100@aliyun.comPurpose: Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms.Patients and Methods: In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy.Results: The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups.Conclusion: Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.Keywords: MTHFR, MTRR, methotrexate, rheumatoid arthritis, DAS28
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spelling doaj.art-b318af2786b44123818057b2e8c472062023-05-02T18:20:13ZengDove Medical PressPharmacogenomics and Personalized Medicine1178-70662023-05-01Volume 1640742383458MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid ArthritisZhang QFu PCao ZHuang HWen QWang KKong TWu XZheng JQian Zhang,1,2 Pan Fu,2 Zhanglei Cao,2 Hua Huang,3 Qinwen Wen,3 Kaizhe Wang,2 Tong Kong,2 Xiudi Wu,3 Jianping Zheng2 1Jiangxi Key Laboratory for Rare Earths Magnetic Materials and Devices, College of Rare Earths, Jiangxi University of Science and Technology, Ganzhou, 341000, People’s Republic of China; 2Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences (CAS), Ningbo, 315300, People’s Republic of China; 3Department of Rheumatology and Immunology, Ningbo First Hospital, Ningbo, 315010, People’s Republic of ChinaCorrespondence: Jianping Zheng; Xiudi Wu, Tel +86– 18091984088 ; +86– 13857826442, Email zhengjianping@nimte.ac.cn; awu1100@aliyun.comPurpose: Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms.Patients and Methods: In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy.Results: The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups.Conclusion: Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.Keywords: MTHFR, MTRR, methotrexate, rheumatoid arthritis, DAS28https://www.dovepress.com/mthfr-and-mtrr-genetic-polymorphism-of-methotrexate-therapy-outcomes-i-peer-reviewed-fulltext-article-PGPMmthfr,mtrr,methotrexate,rheumatoid arthritis,das28
spellingShingle Zhang Q
Fu P
Cao Z
Huang H
Wen Q
Wang K
Kong T
Wu X
Zheng J
MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis
Pharmacogenomics and Personalized Medicine
mthfr,mtrr,methotrexate,rheumatoid arthritis,das28
title MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis
title_full MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis
title_fullStr MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis
title_full_unstemmed MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis
title_short MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis
title_sort mthfr and mtrr genetic polymorphism of methotrexate therapy outcomes in early rheumatoid arthritis
topic mthfr,mtrr,methotrexate,rheumatoid arthritis,das28
url https://www.dovepress.com/mthfr-and-mtrr-genetic-polymorphism-of-methotrexate-therapy-outcomes-i-peer-reviewed-fulltext-article-PGPM
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