one of the prominent challenges of the post - human - genome sequence era is to generate a detailed understanding of inheritable differences in the human genome . structural and functional genetic differences in humans can take the form of single nucleotide polymorphisms ( snp ) , copy number variations ( cnvs ) , and epigenetic or gene expression modifications.[35 ] these inherited inter - individual variations in dna sequence contribute to phenotypic variation , influencing an individual 's anthropometric characteristics , risk of disease and response to the environment . characterizing genetic variation may bring improved understanding of differential susceptibility to disease , differential drug response , and the complex interaction of genetic and environmental factors , which go to produce each phenotype . studying outcomes due to inter - individual differences requires classifying human populations into genotypic or phenotypic cohorts . using demographic background to cluster human populations according to phenotype - representing - genotype has proved challenging . consequently , the design of large scale genotyping projects such as the international hapmap initiative , and their ( future ) applications illustrate the complexities and ambiguities associated with use of group labels in genomic research . attempts to correlate phenotype characteristics associated with ethnicity , geographical division , or disease to genotypes have only had limited success . using ethnicity or race as a basis for phenotypic variation is controversial ; no current approach to identifying phenotypes associated with haplotypes is considered adequate . ayurveda , the traditional system of indian medicine , traditional chinese medicine and korean medicine all have well - defined systems of constitutional types used in prescribing medication bearing distinct similarities to contemporary pharmacogenomics . an interdisciplinary approach integrating genomics and traditional medicine is therefore worth exploring as a search for phenotypes that may collectively be considered for genotyping . this review summarizes research applying a genomic approach to investigate constitutional differences in various traditional systems of medicine from asia . in its holistic foundation , ayurveda uses a threefold classification known as tridosha theory consisting of vata , pitta and kapha dosha for determining a person 's mind - body classification . tridosha theory introduces principles known as vata - related to motion , pitta - related to metabolism and kapha - related to lubrication and structure , to classify phenotypic groupings . elements of vata , pitta and kapha are present in all people , but with differing degrees of predominance . vata ( v ) has kinetic functions , and is manifested in mental functions such as enthusiasm , concentration etc . and physical functions such as respiration , circulation , voluntary actions etc . in modern physiology , mental functions such as intelligence , clear conception and physical phenomena like digestion ; assimilation , heat production , hormones , enzymes and metabolism are attributed to pitta ( p ) . kapha ( k ) manifests in mental functions such as courage , and bodily functions such as tissue building , body strength , immunity , resistance and anabolic activity . v , p and k constitute regulatory systems respectively controlling input / output , turnover and storage making them universal properties of all living systems . doshas are fundamental regulatory principles responsible for maintaining organism functioning and manifesting those characteristics typifying each individual .   in the natural state of equilibrium , all derived ayurvedic concepts concerned with physiology , pathology , diagnosis , prognosis , medicine and therapeutics , are based on the fundamental concepts of v , p , and k dosha phenotypes and their combinations at any given moment . it is held to remain unaltered during the lifetime , having been mostly determined at conception , with contributions from environmental factors including maternal diet and lifestyle . , the prakriti classification of an individual 's constitution is based on differences in physical , physiological and psychological characteristics , and is independent of racial , ethnic or geographical considerations . many individuals can be categorized into one of the three extreme prakriti types , vata , pitta and kapha . subtle combinations of the three v , p , k. prakriti types are as specific and individualized as the dna sequence - based genetic makeup . prakriti specific treatment including medicine , diet and lifestyle is a distinctive feature of ayurveda . we hypothesize that ( 1 ) prakriti has a genetic connotation that can provide a tool for classifying human populations based on broad phenotype clusters , and ( 2 ) the human phenome based on ayurveda can provide a genetic basis for the three major constitutions or prakriti . better characterization of the human genome has improved the scientific basis for understanding individual variation . permutations and combinations of v , p , k attribute characters along with other host factors such as tissue status ( dhatusarata ) , twenty gunas , digestive capacity and metabolic power ( agni ) , psychological nature ( manas prakriti ) , habitat ( desha ) , and season ( kaala ) , lead to sufficient numbers of variants to define a unique constitution for every individual . the importance of such individual variations in assessing states of health and disease was underlined as an important basic principle by charaka some 4000 years ago :  every individual is different from every other and should therefore be considered a different entity ; as many variations are there in the universe , all are seen in human beings . the concept of prakriti plays a central role in understanding health and disease in ayurveda , in a very similar way to the pharmacogenetics that is expected to become the basis of designer medicine . the fundamental principles of the ayurvedic system of medicine can be used to create designer medicines . identifying a genetic basis for functionally , it will involve creating three organized databases capable of intelligently communicating with each other to give a customized prescription , human constitution ( genotype ) , disease constitution ( phenotype ) and drug constitution . the  golden triangle of ayurveda , modern medicine and modern science will converge to form a real discovery engine that can result in newer , safer , cheaper and effective therapies . individuality , genotypes associated with phenotypes , and so classify human populations is therefore important . current classification of human populations is broadly based on ethnicity ; geographical location , language or self reported ancestry . however , such commonly used ethnic labels are inaccurate representations of genetic clusters , and do not reflect underlying genetic makeup . identifying specific phenotypic features and correlating them with genotypes constitutes the major program of phenomics . however there is no consensus on how to define phenotypes , or which phenotypic features are to be included in the database . ayurveda has been investigated for this purpose , based on the hypothesis that prakriti types ( v , p and k ) may offer phenotypic datasets suitable for analysis of underlying genetic variation . as a proof of concept , a first study evaluated 76 subjects both for their prakriti and hla drb1 types , finding significant correlations in support of it . the study concluded that ayurveda based phenomes may provide a model to study multigenic traits , possibly offering a new approach to correlating genotypes with phenotypes for human classification . to prove this hypothesis , more scientific exploration is required ; differential gene expression analysis using micro arrays to identify up and down regulated genes in major prakriti types . such genes could be used for further analysis of dna polymorphism , snp analysis and gene expression in large populations of different ethnic groups . the three major constitution types described in ayurveda have unique putative metabolic activities , k being slow , p fast , while v is considered to have variable metabolism . we hypothesized that this might 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 drug metabolizing enzymes , drug transporters and enzymes involved in dna biosynthesis and repair . poor metabolizer ( pm ) have high plasma concentration of the drug for longer periods and so retain drugs in the body for longer times . extensive metabolizers ( em ) retain drugs in the body for the least time , plasma concentrations being high for shorter periods . metabolic variability in different prakriti types was studied using the drug metabolizing enzymes cyp2c19/cyp2c9 gene polymorphism model . the distribution of cyp2c19 and cyp2c9 genotypes was investigated in 132 healthy individuals of different prakriti classes . em genotypes were predominant in p prakriti while pm genotypes were highest in k. it is interesting to note that * 1/*3 genotype specific to the extensive metabolizer group was present only in p , while the * 2/*3 genotype typical of the poor metabolizer group was observed in k as expected . similarly , in case of gene polymorphism we observed that the occurrence of em genotypes was significantly higher in p prakriti . our study thus demonstrated a probable genomic basis for metabolic differences attributable to prakriti , possibly providing a new approach to pharmacogenomics . genome - wide expression and biochemical differences between ayurveda - based prakriti types have also been studied , revealing differentially expressed genes related to biological processes across different prakriti types . over - expression of genes related to immune response was seen in pitta , whereas the vata group showed differences in expression of genes related to cellular processes . a number of hub genes like tlr-4 , fas , and hla - dqb1 linked to complex diseases , and a few genes like dpyd , abcc1 , and ftl , associated with outcome of cancer treatment , were present in data - sets of genes differentially expressed among prakriti types . despite limitations like small sample size , objectivity in prakriti assessment , use of extreme prakritis and homogenous subject group , this study provides evidence that differences exist across different extreme constitutional types at gene expression level . an attempt was made to integrate ayurveda with functional genomics to identify pathways associated with activity of crude and active components of ashwagandha , a herb used in cancer treatment . sasang constitution medicine ( scm ) is an integral part of traditional korean constitution - based medicine . it recognizes four human constitutions : tae - eum , so - yang , so - eum , tae - yang , into which every human being is categorized , based on physical and physiological attributes . although traditional korean medicine is influenced by traditional chinese medicine , scm emphasizes sociological as well as biological attributes in determining constitutional types . symptomatic observation like healthy state , disease - specific symptoms , major diseases and common symptoms are integral parts of scm diagnosis . individualized medicine is based on assumptions of variations in a. susceptibility to a particular pathological condition , and b. treatment response , similar to the way constitutional medicine is practiced in ayurveda . assumptions include an invariant constitution determined at birth , specific criteria for identifying sasang constitution , and phenotypic variation predicting an underlying genetic basis for scm . genome wide linkage analysis has identified genetic loci on chromosome 8q11.2223 and 11q22.13 , which include 14 labeled genes associated with sasang constitution . further examining the candidate gene loci would help to identify gene variations associated with particular sasang constitutions . to study association of genetic polymorphism in mdr1 with sasang constitution , 270 individuals were genotyped for mdr1 c1236 t , mdr1 g2677t / a and c3435 t . heterozygous mutants for mdr1 c1236 t ( c / t ) occurred with highest frequency for so - eum followed by so - yang . this indicated that individuals with c / t genotype were more likely to be so - eum type . similarly in mdr1 g2677t / a polymorphism wild type allele g was found to be associated with tae - eum type . these results are suggestive of diagnostic value of constitutional types , but further studies are required to examine the effect of these associations on drug metabolism and thus drug response .   according to scm , there is inter - individual difference in susceptibility of an individual to a particular disease and response to a drug . an important finding of one study was that sasang constitution is an independent risk factor for diabetes . prevalence of diabetes was higher in tae - eum ( 11.4% ) followed by so - yang ( 5.0% ) and so - eum ( 1.7% ) . multiple regression showed that tae - eum individuals were at greater risk of developing diabetes than so - eum individuals . angiotensin converting enzyme gene ( ace ) , a candidate gene for cerebral infarction , was studied in different sasang constitutions . although there was no significant association between ace gene polymorphism and cerebral infarction , tae - eum has a higher susceptibility to cerebral infarction than other constitutions , so - eum seems to protect against cerebral infarction . the unique characteristics of scm determination of constitution , based on physical , psychological , symptomatic observation , as well as constitution - based medicine , are in agreement with individualized medicine . further studies using modern technology - based genetic approaches could help establish scm as an alternative to modern personalized medicine . there are several similarities between ayurveda and traditional chinese medicine ( tcm ) including their holistic , individual classification systems . similar to other constitutional medicines , differentiation of constitution is based on differences in physical , physiological and clinical observations . tcm recognizes seven constitutions : normality , yin - deficiency , qi - deficiency , yang - deficiency , phlegm - wetness , wetness - heat , and blood stasis . it assumes five  elements in the material world , earth , water , fire , metal , and wood , movement between which is governed by two opposed qualities of chi energy , yin and yang . a human being is considered a connection between space and earthly elements , while individual health is determined by the state of equilibrium between the two energies , maintained by qi , blood , moisture and essence , the four humors and internal organs . its theory of personalized medicine is a fundamental aspect of tcm , and medicines are prescribed in accordance with a patient 's constitution . tcm recognizes that both susceptibility to disease , and drug response depend on individual constitution . genetic , scientific evidence for tcm 's system of constitution has been elucidated , specifically for associations between different tcm constitutions and polymorphism in hla class ii genes drb1 , dpb1 and dqb1 . frequencies of alleles dpb*0501 were significantly associated with yin - deficiency , drb1 * 09012 with phlegm - wetness , and dqb1 * 03032 allele with the qi - deficiency and phlegm - wetness groups . serological analysis of hla alleles revealed an association between dr*04 and the blood - stasis group , and between dq*09 and the qi - deficiency and phlegm - wetness constitutions . other studies have attempted to address the relationship between traditional medicine constitutions , and hla polymorphism . tcm is found to be effective in treating various complex diseases like diabetes , cancer , alzheimer 's disease , metabolic syndrome , and chronic fatigue syndrome.[3841 ] in parallel to constitution - genomic studies , are those of effects of chinese herbal medicines on genetic regulation . ginseng is considered to be one of the most effective drugs against angiogenesis and related diseases . microarray data revealed the rg1 category of ginsenosides to up - regulate a set of genes responsible for adhesion , and migration processes related to angiogenesis . pharmacogenomic studies are required to investigate genomic pathways involved in physiological effects of ginseng , and other tcm herbal medicines . similarly more studies should be undertaken to investigate possible associations between different genetic markers and constitution . such studies would help make tcm better understood in terms of modern bioscience , promoting more effective integration with modern medicine . traditional japanese medicine has been used for 1500 years and includes kampo - yaku ( herbal medicine ) , acupuncture and acupressure ( shiatsu ) . kampo is now widely practiced in japan and is fully integrated into the modern healthcare system . throughout the history of tcm and kampo , the basic theories and western medicine uses disease - based diagnosis , while tcm and kampo emphasize patient - based diagnosis . it can be characterized as a simplified , positivistic and pragmatic version of chinese herbal medicine . the main theories of kampo are the three substances ( qi , blood , water ) , the eight categories , the five parenchymatous viscera and the six stages of disease . kampo uses a treatment  formulation corresponding to sho ; sho is the patient 's symptoms at a given moment . sho comes from the zheng of tcm , but is simpler because of the simplified kampo theory . sho analyzes a patient 's symptoms terms of qi ( well - being , energy , illness , vigour ) , blood and water ; the eight categories ( yin  yang , hypo- and hyper- function , hot and cold , superficies and interior ) ; the five parenchymatous viscera ; and the six stages of the disease viz . : taiyang , shaoyang , yangming , taiyin , shaoyin , & jueyin . sho may be broadly defined as kampo diagnosis in the epistemic framework of the kampo view of illness . kakkonto sho , denoting symptomatic treatment with kakkonto , to describe sho more precisely . in kampo medicine , the process of diagnosis and treatment is called  formulation corresponding to sho. when treating a patient , kampo practitioners use the sho diagnosis to identify the most suitable formula . the relationship between these steps is compared to that of a lock and key . in this way , every pathological condition is related to its most appropriate prescription . japanese practitioners regard their work as assessing symptoms to identify the disease , so that they can then choose the correct kampo drugs . kampo medicine emphasizes the relationship between the human body and its social and natural environment , and regard any disease state as one of imbalance , which its treatment should correct , by helping patients return to their equilibrium state . it has been reported that exclusively western research models are used to study kampo , and that the approach is compatible with conventional western disease nosology and conventional immunology . hence , it has been proposed that evidence - based kampo medicine should be easily accepted in the west . in contrast to ayurveda , tcm and scm there is a scarcity of literature on genomics and japanese kampo medicine . more studies and further evidence are needed for further integration of understanding of kampo medicine with modern medicine . the traditional systems of medicine in asia ( ayurveda , tcm , scm , kampo ) are considered great living traditions. they are all closely related to each other . all identify unique qualities of each individual , and state the necessity of developing personalized medicine in order to obtain optimal response to treatment . this is similar to the science of pharmacogenomics , which tries to identify individual differences between patients connected to drug metabolism , efficacy and toxicity at the genomic level . in addition to genotype variations , there may be differential expression of genes , copy number variations ( cnvs ) or epigenetic modifications leading to phenotypic variation . omics is focusing on the polygenic approach using high throughput technology rather than the single gene approach . systems biology is an emerging field that aims at system - level understanding of biology through network analyses and molecular interactions . systems biology therefore constitutes a means of bridging the gap between reductionist medicine and traditional medicine  at least partially . using systems biology tools may therefore offer an attractive way to begin to approach the holism of traditional medicine . despite the growing enthusiasm of increasing numbers of western trained doctors for the practice of oriental systems of integrative medicine , there is still a shrill and often vociferous minority , which claims that because the traditional systems do not ( sufficiently yet ) have an adequate empirical or theoretical base , they must be invalid , inconsequential twaddle . traditional systems have to use systematic scientific approach to dismiss these accusations . as regards the human prakriti , or physiological type , the series of experiments reviewed in this paper now demonstrate that it can be empirically validated at the genomics level . at the same time , it is important to acknowledge that the correlations so far observed do almost nothing to prove that individual physiologies have the properties claimed for them in the ancient traditions . obtaining the necessary evidence will require a vastly greater amount of data on thousands of genes for large sample sizes . it could initiate a plethora of scientific projects that will answer crucial questions about the foundations of human physiology , and lay out strategies for developing scientifically validated approaches to preventive medicine , chronic disease care and treatments . under the scheme , the office of principal scientific advisors to government of india , has initiated an ambitious project on genomic variation analysis and gene expression profiling , using principles of ayurveda . this initiative supports robust research with scientific precision , to further elucidate fundamental concepts of ayurveda . not only should it prove valuable in moving the field forward , it may well pioneer the trend for ayugenomics and related traditional medicine research internationally and globally for coming decades .
omics developments in the form of genomics , proteomics and metabolomics have increased the impetus of traditional medicine research . 
 studies exploring the genomic , proteomic and metabolomic basis of human constitutional types based on ayurveda and other systems of oriental medicine are becoming popular . 
 such studies remain important to developing better understanding of human variations and individual differences . 
 countries like india , korea , china and japan are investing in research on evidence - based traditional medicines and scientific validation of fundamental principles . 
 this review provides an account of studies addressing relationships between traditional medicine and genomics .