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pharmocogenomics and genetics in relation with molecular therapeutics and diagnosis
1. Assignment – 01
Pharmacogentics-Genomics in
relation to molecular Diagnosis -
Molecular Therapeutic technologies
By
Narra Naga Pavan Kumar (KVPY Fellow)
1st M.Tech Biotech (14IS1D0301)
Institute of Science & Technology, JNTUK University
2.
3. Interrelation between the pharmacogenomics
and Genetics
• Both are nearly same but the study range is variying
• Pharmacogenomics is the branch of pharmacology that involves the
study of drug response with the entire compliment of genes.
• Pharmacogenetics, refers to study of drug response with a relatively
restricted number of genes.
4. Pharmacogenomics - Genetics
• genome-wide approaches
• more than 1,000,000
polymorphisms
• Study of polymorphisms
• Example :- next generation
Sequenceing
• Gene wide approach
• More then 25, 000 genes
• Study of mutations
• Example :- Microarrays
5. Why the study is needed
• Due the genomic variation
• Due to the environmental factors - Ecogenetics
• Example :- ethanol sensitivity, which is related to acetaldehyde-
dehydrogenase deficiency.
• Due the food we are taking
• Example :- milk intolerance because of lactase deficiency.
• The immune responses of a person
• Toxicogenetics :- Example :- carcinogens
•Results = personalised medicine
8. Personalised medicine
• Personalized medicine is a broad health care that is informed by each
person’s unique clinical, genetic, genomic, and environmental
information to individualizing patient care across the continuum
(from health to disease).
• Goal :- to optimize medical care and outcomes for each individual, to
include treatments, medication types and dosages, and/or prevention
strategies may differ from person to person
9. Therapeutic principles
• All drug effects vary from person to person and all drug effects are influenced by
genes.
• Most drug responses are multifactorial (that is, many genes and many
environmental factors contribute to them).
• Genetic polymorphisms of single genes, including mutations in coding sequences,
gene duplications, gene deletions and regulatory mutations affect numerous drug-
metabolizing enzymes. Several cytochrome-P450 enzymes (for example, CYP2D6
and CYP2C9), N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT)
and UDPglucuronosyltransferases (UDP-GT) are examples. Individuals that possess
these polymorphisms are at risk of experiencing documented adverse reactions or
inefficacy of drugs at usual doses.
10. • Genetic polymorphisms of drug targets and drug transporters are increasingly
recognized (receptors, ion channels, growth factors) as causing variation in drug
responses.
• Several targets of cancer therapy, for example, the epidermal-growth-factor
receptor, respond to treatment only in subgroups of patients who carry sensitizing
mutations of these targets.
• The frequency of variation of drug effects,whether multifactorial or genetic,
varies considerably in ethnically defined populations (for example, alleles of N-
acetyltransferases).
• Application of response-predictive genetic profiles (for example, genotyping for
polymorphisms in antidepressant or cancer-drug therapy) on clinical outcomes
has, so far, been done mostly in academic centres and has not yet reached clinical
practice.
12. Genetic Polymorphisms in Drug Metabolism and
Disposition
• Genetic Polymorphisms in Drug Targets
• Genetic Polymorphisms in Drug Transporters
13. Example :- selection and dosing of chemotherapy
for a patient with acute lymphoblastic leukemia
(ALL)
• Genetic polymorphisms in drug-metabolizing enzymes can have a profound effect
on toxicity and efficacy of medications used to treat ALL and that individualizing
drug dosages can improve clinical outcome.
• It has also been established that the genotype of leukemic lymphoblasts is an
important prognostic variable that can be used to guide the intensity of
treatment.
• all these will be placed on a chip called ALL Chip give the results for a selective
therapy. (reference William E. Evans, et al Science 286, 487, 1999) as same as
microarray technology.
19. References:-
• Genomic and personalized medicine: foundations and applications GEOFFREY S.
GINSBURG et al., Translational Research December 2009;272 – 287.
• Molecular Genetic Markers as A Basis for Personalized Medicine Sonja Pavlovi et
al., J Med Biochem 33: 8–21, 2014.
• Pharmacogenetics: data, concepts and tools to improve drug discovery and drug
treatment Jürgen Brockmöller et al., Eur J Clin Pharmacol (2008) 64:133–157.
• Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics
William E. Evans, et al. Science 286, 487 (1999).
• Pharmacogenetics – five decades of therapeutic lessons from genetic diversity,
Urs A.Meyer, Nature Reviews Genetics September 2004, vol 4, 669 -676