Abstract
BackgroundDNA methylation and its perturbations are an established attribute to a wide spectrum of phenotypic variations and disease conditions. Indian traditional system practices personalized medicine through indigenous concept of distinctly descriptive physiological, psychological and anatomical features known as prakriti. Here we attempted to establish DNA methylation differences in these three prakriti phenotypes.MethodsFollowing structured and objective measurement of 3416 subjects, whole blood DNA of 147 healthy male individuals belonging to defined prakriti (Vata, Pitta and Kapha) between the age group of 20-30years were subjected to methylated DNA immunoprecipitation (MeDIP) and microarray analysis. After data analysis, prakriti specific signatures were validated through bisulfite DNA sequencing.ResultsDifferentially methylated regions in CpG islands and shores were significantly enriched in promoters/UTRs and gene body regions. Phenotypes characterized by higher metabolism (Pitta prakriti) in individuals showed distinct promoter (34) and gene body methylation (204), followed by Vata prakriti which correlates to motion showed DNA methylation in 52 promoters and 139 CpG islands and finally individuals with structural attributes (Kapha prakriti) with 23 and 19 promoters and CpG islands respectively. Bisulfite DNA sequencing of prakriti specific multiple CpG sites in promoters and 5′-UTR such as; LHX1 (Vata prakriti), SOX11 (Pitta prakriti) and CDH22 (Kapha prakriti) were validated. Kapha prakriti specific CDH22 5′-UTR CpG methylation was also found to be associated with higher body mass index (BMI).ConclusionDifferential DNA methylation signatures in three distinct prakriti phenotypes demonstrate the epigenetic basis of Indian traditional human classification which may have relevance to personalized medicine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0506-0) contains supplementary material, which is available to authorized users.
Highlights
DNA methylation at cytosine bases of CpG dinucleotide is an epigenetic phenomenon widely used to regulate gene expression in humans [1]
Intra-prakriti methylation analysis The intra-prakriti methylated probes were identified by providing a cutoff of fold change (FC) ≥1.5 with 5% false discovery rate (FDR), based on the previous reports [30,37]
Our study showed that large proportions of DNA methylation patterns are common between prakritis; observed differences in methylation signatures between prakriti suggests the presence of different mechanisms that may influence and sustain the expression of key regulator genes involved in the manifestation of distinct phenotypes
Summary
DNA methylation at cytosine bases of CpG dinucleotide is an epigenetic phenomenon widely used to regulate gene expression in humans [1]. The broad classification of phenotypic variations based on physiological, anatomical and psychological evaluation. Ayurveda suggests that principles of these evaluations are the basis of individuals life course and health events established at birth or prakriti which can be identified as Vata, Pitta and Kapha phenotypes with discrete characteristics [11,12]. The human classifications based on the body constitution as Vata, Pitta and Kapha prakriti in Ayurveda has formed the basis of disease management and for practicing traditional personalized medicine [13]. Indian traditional system practices personalized medicine through indigenous concept of distinctly descriptive physiological, psychological and anatomical features known as prakriti. We attempted to establish DNA methylation differences in these three prakriti phenotypes
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