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Pharmacogenomics of Autoimmune Diseases

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Omics for Personalized Medicine

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Abstract

Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis cause a considerable degree of morbidity worldwide. Although the treatment of these conditions has shown progress over the last decade with the steady trickle of new drug molecules, drug therapy is far from satisfactory due to the reduced efficacy and maximal toxicity in certain patients. Several factors are known to influence the efficacy and toxicity of these drugs such as age, gender, liver and kidney function, and concomitant drug therapy. Another crucial factor influencing drug response of the patient is the genetic constitution of the patient. For example, polymorphisms in the gene MTHFR such as 677T>C can increase methotrexate serum levels and lead to toxicity in a patient with RA. Similarly polymorphisms in the drug transporter ABCB1 are associated with decreased efficacy to methotrexate. Polymorphisms within the TNF promoter region have been shown to modify the clinical efficacy and toxicity of anti-TNF therapy in RA patients. SLE patients with polymorphic TPMT gene may require a reduced dose of azathioprine to circumvent the catastrophe of fatal bone marrow suppression. Polymorphisms in the TYMS gene could lead to reduced efficacy with methotrexate in psoriatic arthritis patients. Although our understanding of autoimmune diseases has improved considerably over the last decade and several studies in pharmacogenomics of autoimmune diseases have been carried out, the only clinical application is TPMT testing for azathioprine. Yet with improved methodology adopted in pharmacogenomics studies coupled with novel technologies, the field of pharmacogenomics does appear to offer significant promise in the coming years towards the dream of personalized medicine in autoimmune diseases.

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Authors and Affiliations

  1. Department of Cardiology, SRM Medical College and Hospital Research Centre, Kattankulathur, Kancheepuram District, Tamil Nadu, India

    Melvin George MD., DM.

  2. Division of Clinical Pharmacology, JIPMER, Pondicherry, India

    Sandhiya Selvarajan & Suresh Kumar Srinivasamurthy

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  1. Melvin George MD., DM.
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  2. Sandhiya Selvarajan
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  3. Suresh Kumar Srinivasamurthy
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Correspondence to Melvin George MD., DM. .

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Editors and Affiliations

  1. Centre for Genomics & Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Purba Medinipur, West Bengal, India

    Debmalya Barh

  2. Institute of Life Sciences, B.V. Patel Pharmaceutical Education and Research Development Centre, Ahmedabad University, Ahmedabad, Gujarat, India

    Dipali Dhawan

  3. Policy Centre for Biomedical Research, Translational Health Science and Technology Institute (Department of Biotechnology Institute, Government of India), Office @ National Institute of Immunology, New Delhi, India

    Nirmal Kumar Ganguly

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George, M., Selvarajan, S., Srinivasamurthy, S.K. (2013). Pharmacogenomics of Autoimmune Diseases. In: Barh, D., Dhawan, D., Ganguly, N. (eds) Omics for Personalized Medicine. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1184-6_13

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