학술논문
DNA methylation analysis of phenotype specific stratified Indian population.
Document Type
Article
Author
Rotti, Harish; Mallya, Sandeep; Kabekkodu, Shama Prasada; Chakrabarty, Sanjiban; Bhale, Sameer; Bharadwaj, Ramachandra; Bhat, Balakrishna K.; Dedge, Amrish P.; Dhumal, Vikram Ram; Gangadharan, G. G.; Gopinath, Puthiya M.; Govindaraj, Periyasamy; Joshi, Kalpana S.; Kondaiah, Paturu; Nair, Sreekumaran; Nair, S. N. Venugopalan; Nayak, Jayakrishna; Prasanna, B. V.; Shintre, Pooja; Sule, Mayura
Source
Subject
*DNA methylation
*GENE expression
*LIQUID chromatography
*POTASSIUM dihydrogen phosphate
*BONFERRONI correction
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Language
ISSN
1479-5876
Abstract
Background: DNA 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. Methods: Following 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. Results: Differentially 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 alsofound to be associated with higher body mass index (BMI). Conclusion: Differential DNA methylation signatures in three distinct prakriti phenotypes demonstrate the epigenetic basis of Indian traditional human classification which may have relevance to personalized medicine. [ABSTRACT FROM AUTHOR]