Traditional Medicine to Modern Pharmacogenomics: Ayurveda Prakriti Type and CYP2C19 Gene Polymorphism Associated with the Metabolic Variability

Evidence-Based Complementary and Alternative Medicine, Jun 2011

Traditional Indian medicine—Ayurveda—classifies the human population into three major constituents or Prakriti known as Vata, Pitta and Kapha types. Earlier, we have demonstrated a proof of concept to support genetic basis for Prakriti. The descriptions in Ayurveda indicate that individuals with Pitta Prakriti are fast metabolizers while those of Kapha Prakriti are slow metabolizers. We hypothesized that different Prakriti may have different drug metabolism rates associated with drug metabolizing enzyme (DME) polymorphism. We did CYP2C19 (Phase I DME) genotyping in 132 unrelated healthy subjects of either sex by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We observed significant association between CYP2C19 genotype and major classes of Prakriti types. The extensive metabolizer (EM) genotype (*1/*1, *1/*2, *1/*3) was found to be predominant in Pitta Prakriti (91%). Genotype (*1/*3) specific for EM group was present only in Pitta Prakriti. Poor metabolizer (PM) genotype (*2/*2, *2/*3, *3/*3) was highest (31%) in Kapha Prakriti when compared with Vata (12%) and Pitta Prakriti (9%). Genotype (*2/*3) which is typical for PM group was significant in Kapha Prakriti (odds ratio = 3.5, P =  .008). We observed interesting correlations between CYP2C19 genotypes and Prakriti with fast and slow metabolism being one of the major distinguishing and differentiating characteristics. These observations are likely to have significant impact on phenotype-genotype correlation, drug discovery, pharmacogenomics and personalized medicine.

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Traditional Medicine to Modern Pharmacogenomics: Ayurveda Prakriti Type and CYP2C19 Gene Polymorphism Associated with the Metabolic Variability

Traditional Medicine to Modern Pharmacogenomics: Ayurveda Prakriti Type and CYP2C19 Gene Polymorphism Associated with the Metabolic Variability Yogita Ghodke,1 Kalpana Joshi,2 and Bhushan Patwardhan1 1Bioprospecting Laboratory, Interdisciplinary School of Health Sciences, University of Pune, India 2Department of Biotechnology, Sinhagad College of Engineering, Pune 411041, India Received 17 November 2008; Accepted 10 November 2009 Copyright © 2011 Yogita Ghodke et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Traditional Indian medicine—Ayurveda—classifies the human population into three major constituents or Prakriti known as Vata, Pitta and Kapha types. Earlier, we have demonstrated a proof of concept to support genetic basis for Prakriti. The descriptions in Ayurveda indicate that individuals with Pitta Prakriti are fast metabolizers while those of Kapha Prakriti are slow metabolizers. We hypothesized that different Prakriti may have different drug metabolism rates associated with drug metabolizing enzyme (DME) polymorphism. We did CYP2C19 (Phase I DME) genotyping in 132 unrelated healthy subjects of either sex by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We observed significant association between CYP2C19 genotype and major classes of Prakriti types. The extensive metabolizer (EM) genotype (*1/*1, *1/*2, *1/*3) was found to be predominant in Pitta Prakriti (91%). Genotype (*1/*3) specific for EM group was present only in Pitta Prakriti. Poor metabolizer (PM) genotype (*2/*2, *2/*3, *3/*3) was highest (31%) in Kapha Prakriti when compared with Vata (12%) and Pitta Prakriti (9%). Genotype (*2/*3) which is typical for PM group was significant in Kapha Prakriti (odds ratio = 3.5, P =  .008). We observed interesting correlations between CYP2C19 genotypes and Prakriti with fast and slow metabolism being one of the major distinguishing and differentiating characteristics. These observations are likely to have significant impact on phenotype-genotype correlation, drug discovery, pharmacogenomics and personalized medicine. 1. Introduction Ayurveda remains one of the most ancient and yet living traditions documented and practiced widely in India [1]. It has a time-honored philosophical and experiential basis. The core concept of health and disease in Ayurveda is built around the uniqueness of an individual [2]. Ayurveda uses a 3-fold classification known as tridosha theory that identifies principles of motion (Vata), metabolism (Pitta) and structure (Kapha) as discrete phenotypic groupings [3]. According to Ayurveda, the individual constitution or Prakriti classification is based on differences in physical, physiological and psychological characteristics and is independent of racial, ethnic or geographical considerations. The importance of such individual variations in health and disease is an important basic principle rightly described hundreds of years ago as “every individual is different from another and hence should be considered as a different entity; as many variations are there in the Universe, all are seen in the human being" [4–6]. The doshas exhibit more easily recognizable phenotypes. Evidence-based research in Ayurveda is receiving larger acceptance in India and abroad [7–9]. According to Ayurveda, Prakriti of an individual is determined at the time of conception and remains unaltered during the lifetime. Prakriti-specific treatment including medicine, diet and lifestyle is a distinctive feature of Ayurveda [10]. We hypothesized that Prakriti has a genetic connotation that can provide a tool for classifying human population based on broad phenotype clusters. We hypothesize that the human phenome based on Ayurveda can provide a genetic basis for the three major constitutions or Prakriti. Earlier, in a pilot study, we evaluated 76 subjects both for their Prakriti and HLA DRB1 typing. We observed a significant correlation between certain HLA types and Prakriti types [11]. For better validation, the homologous relation of Vata (V), Pitta (P) and Kapha (K) to human genetic structure requires further study [12]. Three major constitution types as Vata, Pitta and Kapha Prakriti have unique putative metabolic activities. Kapha is slow, Pitta is fast, while Vata is considered to have variable metabolism. We hypothesize that this may relate to drug metabolism and genetic polymorphism of drug metabolizing enzymes (DME). Inter-individual variability in drug response can be attributed to polymorphism in genes encoding different DMEs, drug transporters and enzymes involved in DNA biosynthesis and repair [13, 14]. Mutation in gene coding for DMEs may result in variants with high, low or no activity. Major genetic polymorphisms affecting DME activity are related to drug oxidation by (...truncated)


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Yogita Ghodke, Kalpana Joshi, Bhushan Patwardhan. Traditional Medicine to Modern Pharmacogenomics: Ayurveda Prakriti Type and CYP2C19 Gene Polymorphism Associated with the Metabolic Variability, Evidence-Based Complementary and Alternative Medicine, 2011, 2011, DOI: 10.1093/ecam/nep206