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Reduced folate carrier-1 80G > A gene polymorphism is not associated with methotrexate treatment response in South Indian Tamils with rheumatoid arthritis

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Abstract

Methotrexate (MTX) is the most commonly used disease-modifying drug to treat rheumatoid arthritis (RA). Although there are no reliable molecular markers to predict the treatment response and adverse effects to MTX therapy, the polymorphisms in genes coding for MTX metabolizing enzymes and transporters may play a crucial role. The reduced folate carrier-1 (RFC-1) is a bidirectional anion exchanger which transports MTX and folinic acid. It is reported to influence MTX treatment response and adverse effects in some ethnic populations but not in others. It is also associated with susceptibility to various diseases including systemic lupus erythematosus (SLE). The present study was aimed at investigating the role of RFC-1 80G > A gene polymorphism in association with disease susceptibility, MTX treatment response and the MTX-induced adverse events in the South Indian Tamil patients with rheumatoid arthritis. The RFC-1 80G > A gene polymorphism was investigated in 327 patients with RA and in 322 healthy controls by PCR-RFLP method. It was found that the heterozygous RFC-1 80 GA genotype was associated with protection against RA [p = 0.02, odds ratio (OR) 0.69, 95 % confidence interval (CI) 0.50–0.95]. However, it was not found to be associated with MTX treatment response. The RFC-1 G allele frequency was higher in patients with adverse effects, but the difference was not statistically significant (p = 0.08, OR 1.44, 95 % CI 0.97–2.13). RFC-1 80G > A gene polymorphism confers protection for RA. However, it is not associated with MTX treatment response and MTX-induced adverse effects in South Indian Tamil patients with RA.

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Abbreviations

ACPA:

Anticitrullinated peptide antibody

ACR:

American College of Rheumatology

AIRE:

autoimmune regulator

DAS28:

(ESR) score Disease activity score based on 28 joints and erythrocyte sedimentation rate

DMARD:

Disease-modifying antirheumatic drug

HLADR:

Human leukocyte antigen

MAF:

Minor allele frequency

MHC2TA:

Major histocompatibility complex II transactivator

PCR:

Polymerase chain reaction

RA:

rheumatoid arthritis

RF:

Rheumatoid factor

RFC:

Reduced folate carrier

RFLP:

Restriction fragment length polymorphism

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Acknowledgments

The study was supported by an intramural research grant by JIPMER, Puducherry, India. In addition, the infrastructure and other support provided by DST-FIST and ICMR-INSERM programs are also acknowledged.

Author Contributions

VSN conceived and planned the study. NM performed the laboratory work with the precious help of CMM. NM performed statistical analysis.VSN and MCB recruited the patients, collected, organized, and interpreted the clinical data. VSN and NM wrote the manuscript. VSN coordinated the research and critically reviewed the manuscript and takes the primary responsibility for the article.

Conflict of interest

All authors declare that there are no conflicts of interest.

Ethical standards

The study was carried out in compliance with international, national, and institutional regulations. Institute Ethics Committee has approved the study. All persons gave informed consent prior to the inclusion in the study.

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Authors and Affiliations

  1. Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India

    Niveditha Muralidharan, Christina Mary Mariaselvam, Mithun CB & Vir Singh Negi

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  1. Niveditha Muralidharan
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  2. Christina Mary Mariaselvam
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  3. Mithun CB
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  4. Vir Singh Negi
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Correspondence to Vir Singh Negi.

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Muralidharan, N., Mariaselvam, C.M., CB, M. et al. Reduced folate carrier-1 80G > A gene polymorphism is not associated with methotrexate treatment response in South Indian Tamils with rheumatoid arthritis. Clin Rheumatol 35, 879–885 (2016). https://doi.org/10.1007/s10067-015-2917-y

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  • DOI: https://doi.org/10.1007/s10067-015-2917-y

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