MTHFR Gene Polymorphism As A Predictor In Determining Drug Toxicity

Abstract

Variations in response to a drug are a major clinical issue for therapeutics with newlinenarrow range such as methotrexate (MTX). MTX is the best tolerated and extensively newlineused disease modifying anti-rheumatic drug (DMARD) for treating several disorders newlineincluding rheumatoid arthritis (RA). In spite of its high clinical effects in the newlinemanagement of various diseases, toxicity becomes the principal reason for the newlinediscontinuation of the drug which ultimately affects disease outcome. There are newlinecurrently no pharmacogenetic tests in clinical practice for predicting toxicity events that newlinemay be induced upon MTX adminstration. Pharmacogenetic analysis of genetic newlinepolymorphism within the genes regulating metabolic pathway associated with the mode newlineof action of the drug can provide meaningful evidences which can fill this gap. newlineApart from the therapeutic effect, MTX has great impact on intracellular folate newlinemetabolism that influences the enzyme activity of methylene tetrahydrofolate reductase newline(MTHFR). MTHFR is one of the essential enzyme that regulates folic acid pathway. newlineThere are several evidences that suggest the association of MTX induced toxicity with newlinesingle nucleotide polymorphism (SNP) in the genes encoding MTHFR. The main newlineobjective of the study was to find out the influence of MTHFR C677T and A1298C newlinegene polymorphism on MTX induced toxicity, disease outcome and survival of the newlinepatients. newlineWhile intruding into the literature several factors were found associated with the newlineincidence of drug toxicity. Vitamin D was found to be an essential micronutrient which newlineregulates a number of biological pathways and reported with immuno-modulatory newlineactivity. Similarly, osteopontin (OPN), a pro-inflammatory cytokine found to be newlineassociated with inflammation and disease severity. Therefore, the study investigated newlineassociation of vitamin D with OPN and other serological parameters which are newlineindicators of several kinds of toxicity and disease activity. newlineDuring the course of study, disease was found more prevalent in females than newlinemales. So, this piece of