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Prakṛti (Constitutional Types)

Though tridosa is ubiquitous, it exists in individuals in differing magnitudes, in the state of health. This is called prakrti, which is literally translated as “nature”. When the prakrti of an individual is challenged by dietary or behavioral indiscretions and exteroceptive factors, vikrti or “distortion” appears, resulting in disease. Based on the season in which conception occurs, dietary and behavioral patterns of the pregnant mother, dominance of tridosa in the mother’s reproductive tract and genetic factors, individuals are born with a characteristic physiological constitution (prakrti). As there can be innumerable combinations of tridosa, there can be innumerable prakrti. However, as it is humanly impossible to comprehend an endless array of prakrti, Ayurveda advises that a physician need to consider only seven prakrti, namely, vata prakrti, pitta prakrti, kapha prakrti, vata- pitta prakrti, vdta-kapha prakrti, pitta-kapha prakrti and vata-pitta-kapha (homologous) prakrti. These seven types are discernible by typical physical, behavioral and psychological characteristics. As individuals belonging to each prakrti are prone to diseases arising out of the destabilization of the corresponding component (s) of tridosa, food, measures and medicinal substances should be selected to promote their steady state and maintain health (Upadhyaya 1975c).

Understanding Prakṛti

The first empirical test providing preliminary statistical support to the concept of prakrti was carried out by Joshi (2004). Using regression modeling with a sample of 117 healthy subjects (ages 18-70), she created an algorithmic heuristic based on physical and psychological characteristics traditionally used by ayurvedic physicians to determine prakrti. This heuristic was compared with the qualitative assessment of prakrti for each of the subject and found a 75% convergence with significance at the p = 0.05 level. This study was flawed in that it did not specify gender variation within the sample set, and the diagnostic criteria used by the ayurvedic physicians were not specified. Nevertheless, this test is considered to be one of the pioneering studies on the theoretical constructs of Ayurveda.

The human leukocyte antigen (H.L.A.) system is a gene complex encoding the major histocompatibility complex (M.H.C.) proteins in human beings. These proteins found on the cell surface are responsible for the regulation of the immune system. H.L.A. genes are highly polymorphic and they have many different alleles (mutants of a gene found at the same place on a chromosome), allowing greater efficiency of the adaptive immune system (Svejgaard 1978; Bodmer 1997; Jin and Wang 2003).

Patwardhan et al. (2005) made an attempt to correlate characteristics of prakrti with genotypes (groups of individuals with the same inherited map carried within the genetic code). They evaluated the prakrti of 76 subjects and then determined their H.L.A. DRB1 types using low- resolution polymerase chain reaction sequence-specific primers and oligonucleotide probes. 14 alleles were examined. A reasonable correlation was observed between H.L.A. types and prakrti types. H.L.A. DRB1*02 allele was completely absent in the vat a type and H.L.A. DRB1*13 was absent in the kapha type. Moreover, H.L.A. DRB1*10 allele had higher allele frequency in the kapha type than in the pitta and vata types. This finding indicates that there is immunological difference between the various prakrti types. Though limited by a small sample size and lack of diversity in the sample set, this study is the first attempt to understand the concept of prakrti using tools of molecular biology.

Gene Polymorphism of Drug Metabolizing Enzyme

A few reports have appeared in recent years suggesting that differences in physiological responses are shown by individuals belonging to the major types of prakrti. The concept of prakrti revolves around discrete phenotypic groupings based on the principles of motion (vata), metabolism (pitta) and structure (kapha) (Hankey 2005; Rhoda 2014). As inter-individual variability in drug response can be attributed to polymorphism in genes encoding different drug metabolizing enzymes, drug transporters and enzymes involved in D.N.A. biosynthesis (Evans 2003; Evans and McLeod 2003), distribution of these genotypes can be a good tool for studying the biochemical basis of prakrti.

Ghodke et al. (2011) studied the gene polymorphism of the CYP2C19 gene involved in metabolism of many drugs (Goldstein and de Morais 1994: Daly 1995) in 132 unrelated healthy subjects. Significant association was observed between CYP2C19 genotype and major classes of prakrti types. The extensive metabolizer (EM) genotype (*1/*1, *l/*2, *T/*3) was found to be predominant in pitta prakrti (91%). Genotype (*l/*3) specific for EM group was present only in pitta prakrti. The poor metabolizer (P.M.) genotype (*2/*2, * 2ЛЗ, *3/*3) was highest (31%) in kapha prakrti when compared with vata (12%) and pitta prakrti (9%). Genotype (*2/*3) which is typical of the P.M. group was significant in kapha prakrti. The authors observed interesting correlations between CYP2C19 genotypes and prakrti, with fast and slow metabolism being one of the major distinguishing and differentiating characteristics.

Whole Genome Expression and Biochemical Correlates

Prasher et al. (2008) carried out an interesting study to explore whether the prakrti types have any molecular basis. 96 unrelated healthy individuals with predominance of vata (n = 39), pitta (n = 29) or kapha (n = 28) were included in the study. Peripheral blood samples of the subjects were collected and 33 biochemical tests used in routine diagnostics were performed on the blood samples. The samples were also analyzed for genome wide expression levels. Gene ontology and pathway- based analysis were carried out on differentially expressed genes to find out if there were significant enrichments of functional categories among prakrti types.

Individuals of different prakrti exhibited differences in biochemical components. From the 33 biochemical parameters, 15 parameters in males and 4 in females showed significant differences with respect to prakrti. Interestingly, components of lipid profile like triglycerides, total cholesterol, V.L.D.L., L.D.L., L.D.L./H.D.L. ratio, were higher in kapha when compared to pitta and vata males. Kapha prakrti also had lower levels of H.D.L. when compared to the vata counterpart. The levels of serum uric acid, considered to be an independent predictor of cardiovascular mortality, were also found to be elevated in kapha prakrti. G.G.P.T., S.G.P.T. and serum zinc were also high in the kapha group. Serum prolactin and prothrombin time were high in the vata group when compared to the kapha or pitta groups. On the other hand, pitta type males showed high values of hematological parameters like hemoglobin, P.C.V. and R.B.C. count in comparison to vata and/or kapha groups (Prasher et al. 2008).

Analysis of genome-wide expression through c.D.N.A. microarrays, using independently pooled samples of vata, pitta and kapha males and females in a set of loop design experiments, unraveled a number of differentially expressed genes in each category. Among the 8416 annotated genes in the 19K array (CA Ontario), 159 in males and 92 in females were found to be differentially expressed. Amongst the differentially expressed genes there was a significant over-representation of hub genes associated with complex diseases and housekeeping genes related to basic cellular function (Prasher et al. 2008).

EGLN1 was one of the 251 differentially expressed genes among the prakrti types (Prasher et al. 2008). In a follow-up study Aggarwal et al. (2010) reported a link between high-altitude adaptation and common variations rs479200 (C/T) and rs480902 (T/C) in the EGLNI gene. Additionally, the TT genotype of rs479200, which was more frequent in kapha types and correlated with higher expression of EGLNI, was associated with patients suffering from high-altitude pulmonary edema. However, it was present at a significantly lower frequency in pitta and almost absent in dwellers of high altitude. Analysis of the Human Genome Diversity Panel, Centre d’Etude du Polymorphisme Humain and Indian Genome Variation Consortium panels showed that dissimilar genetic lineages at high altitudes share the same ancestral allele (T) of rs480902 that is over-represented in pitta and positively correlated with altitude globally. Therefore, it can be inferred that EGLNI polymorphisms are associated with high-altitude adaptation (also see Yi et al. 2010; Simonson et al. 2010; Storz 2010). A genotype rare in highlanders but over-represented in the kapha prakrti subgroup of normal lowlanders may render them more prone to high-altitude pulmonary edema. The authors concluded that genetic analysis of healthy individuals phenotyped using the principles of Ayurveda could uncover genetic variations associated with adaptation to external environment and susceptibility to diseases.

Genetic Basis of Prakṛti

A single-nucleotide polymorphism (S.N.P.) is a variation in a single nucleotide that occurs at a specific position in the genome. Though a particular S.N.P. may not cause a disorder, some S.N.P.s are associated with certain diseases. S.N.P.s can be useful tools to evaluate an individual’s genetic predisposition to develop a disease (Syvanen 2001). Govindaraj et al. (2015) reported correlation of genomic variations with the classification of prakrti. They performed genome-wide S.N.P. analysis of 262 well-classified male subjects, belonging to the three prakrti. These subjects were recruited from screening a population of 3416 individuals. It was found that 52 S.N.P.s were significantly different between the three prakrti. On the basis of principal component analysis, these S.N.P.s could be classified into their respective vata, pitta and kapha prakrti groups. 52 clusters of differentiation (C.D.) markers were used to find the genotype-phenotype correlations. Marker rsl0518915 was found to be associated with vata and pitta prakrti, whereas rs986846 was found to be associated with kapha and vata prakrti. 4 markers (rs2269241, rs2269240. rs2269239, rs2269238) of the PGMlgene were associated with pitta prakrti. This study suggests that the phenotypic classification (prakrti) in Ayurveda has a genetic basis.

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