Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda

Abstract

Background: Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates.

Methods: Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types.

Results: Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types.

Conclusion: Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine.

Figure 1

Loop design of microarray experiment. V, P, K represent Vata, Pitta, Kapha and arrow head and tail indicate Cy3 and Cy5 respectively. In one set of experiment comprising of three slides each Prakriti has been labelled with Cy3 or Cy5 and hybridised to the other two Prakriti samples labelled with the opposite dye.

Figure 2

Differentiating biochemical and hematological profile between and Prakriti groups. Data shown is based on biochemical and hematological profile differences in distinct Prakriti groups – "Vata" (V), "Pitta" (P) and "Kapha" (K). Signs "-"and "+" refers to lower and higher values respectively. Heat map (made using Cluster and Tree View) represented in Figures (A) and (B) depicts significant differences in male and female respectively. "*" indicates parameters with non normal distribution. These have been compared using Kruskal-Wallis Test.

Figure 3

Differentiating genome wide expression profile between Prakriti groups. Data shown is based on Gene Ontology Biological Process (GOBP) category enrichments in distinct Prakriti groups – "Vata" (V), "Pitta" (P) and "Kapha" (K). Each column defines profiles based on their unique expression in one Prakriti compared to the other two. For instance "P-" refers to down-regulation in Pitta when compared to Vata and Kapha and vice versa for "P+". Heat map (made using Cluster and Tree View) represented in Figures (A) and (B) depicts significant GOBP enrichments in male and female respectively.