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WHAT ELSE DID I INHERIT? (GENETIC VARIATION IN DRUG METABOLISM AMONGST VARIOUS ETHNIC GROUPS) Annette Youssef Pharm D. Candidate 2010 June 25, 2009.

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Presentation on theme: "WHAT ELSE DID I INHERIT? (GENETIC VARIATION IN DRUG METABOLISM AMONGST VARIOUS ETHNIC GROUPS) Annette Youssef Pharm D. Candidate 2010 June 25, 2009."— Presentation transcript:

1 WHAT ELSE DID I INHERIT? (GENETIC VARIATION IN DRUG METABOLISM AMONGST VARIOUS ETHNIC GROUPS) Annette Youssef Pharm D. Candidate 2010 June 25, 2009

2 Outline Project Proposal US Census Information The Founder Effect Niche in GeneMedRx Data Collection Methods Genotype Phenotype Calculations Data Presentation Significant Ethnic Variations in Drug Metabolism

3 Project Proposal Compile data on frequency of genetic variation in drug metabolizing enzymes in individual ethnic groups Predict varying degrees of drug metabolism amongst individual ethnic groups by converting genotype information into phenotype information Input this information into GeneMedRx Create Drug-Ethnic Group interaction Make Available to healthcare providers and patients

4 SEGREGATION OF ETHNIC GROUPS Countrys Borders Cultural Boundaries Language Religion Child Rearing Social Network: Work & School Settlement Economical Reasons: Endogamy & Cousin Couples: Contain land and property in the family Popular saying amongst Middle Eastern and Mediterranean cultures: The girl is for her cousin Limited Mobility Rising Gas Prices Government Policies: Embargos Xenophobia Invisible Boundaries Others

5 MERGING OF ETHNIC GROUPS Merging Borders: The European Union Migration United States Termed: The Melting Pot Technology Rapid Travel Rapid Communication: Internet, Satellite, Telephone Global Market Travel Business School: Study Abroad Military Leisure Acceptance of Other Cultures International Cuisine Alternative Therapies: Yoga, Acupuncture, Cupping

6 US Census Data Country United States United States: Foreign born as a percentage of the total population, 1990 and 1994 to 2006 *The 1994 to 2005 estimates presented in this table were derived from the US Census Bureau Current Population Survey (CPS). The 1990 & 200 data were derived from the 1990 & 2000 US Census of Population and Housing.

7 US CENSUS DATA 2000 RACE % One race ………......… White …… ……….… Hispanic/Latino Mexican …… Puerto Rican Cuban …… Other Hispanic/Latino ………….… Black/African American …………..…10.8 Native American/Alaska…………… Asian …………….…..3.2 Asian Indian …….. …0.5 Chinese ….....…..0.8 Filipino …...… 0.6 Japanese …. …..0.3 Korean …… Vietnamese …… Other Asian … Native Hawaiian/Pacific Islander. …..0.1 Native Hawaiian … Guamanian or Chamorro.... ….. … - Samoan … Other Pacific Islander …… - Some other race …….… Two or more races …

8 US Census Data Although ~10% of the US population was foreign born in 2000, only 2.4% of the US population had a mixed racial background The melting pot may not be an accurate description of the US Refers to the predicted homogeneity that would result from the influx of immigrants especially in the early 1900s

9 Founder Effect Definition: when a population is established by a very small number of individuals from a larger population

10 Founder Effect Results: In loss of genetic variation Subpopulation is genetically and phenotypically different from the larger population Thought to lead to speciation in extreme cases Genetic diversity amongst ethnic groups is a watered down version of the Founder Effect

11 NICHE IN GENEMEDRX Patient Histories: Record: Race/ethnicity already included in patient information sheets Current Use: Retrospective Medical Statistics Patient Identification Current Use: Prospective (minimally) Hypertension in Black Patients: Calcium Channel Blockers & Diuretics vs. ACE-I or Beta Blockers Crestor (rosuvastatin) in Asians: Greater degree of rhabdomylosis; choose different statin Use in GeneMedRx: Prospective Drug-Ethnic Background Interaction

12 NICHE IN GENEMEDRX Drug-Ethnic Background Interaction Display: Frequency of phenotype expression of drug metabolizing enzyme in a chosen ethnic group Display: Will Interact with the metabolism information for a certain drug Information Utilization: When frequency of variation in drug metabolism is high: Begin with a different dose (GeneMedRx Program) Choose alternative drug (GeneMedRx Program) Order a genetic test (Genelex)

13 GeneMedRx Now and After GeneMedRx Now: Can only predict a drug-gene interaction if someone has previously been genetically tested Predicts drug-drug interactions: other programs which already do this (Clinical Pharmacology)

14 GeneMedRx Now and After GeneMedRx After: Increase awareness of genetic variation Increase subscription to GeneMedRx: help recommend drug therapy in different ethnic groups May increase likelihood of ordering a genetic test Intelligent Genetic Testing: Prescriber can recommend genetic testing when appropriate Insurance Companies: Increase likelihood of paying for a genetic test if circumstances are appropriate To avoid cost of hospitalization due to adverse effects (Active Drug) To avoid cost of drug that is not effective (Prodrug)

15 DATA COLLECTION PubMed Search: Kew Words: Allele, Frequency, Genetic, Polymorphisms, Metabolism, Ethnic, Racial, CYP___, Variation Data Selection: All abstracts and full text articles that had genotype or allelic frequency data on particular cytochrome metabolizing enzyme of interest

16 Allele Frequency Genotype Phenotype Poor Metabolizer (1 Condition): Loss of function allele x loss of function allele Intermediate Metabolizer (3 Conditions): Reduced function allele x loss of function allele Functional allele x loss of function allele Reduced function allele x reduced function allele Extensive Metabolizer (2 Conditions): Reduced function allele x fully functional allele Fully functional allele x fully functional allele Ultra Rapid Metabolizer (2 Conditions): 3 or more copies of functional alleles 1 or more copies of alleles associated with tighter binding of substrate than fully functional allele

17 Alleles Loss of Function: Little or no ability to metabolize a substrate (drug and/or metabolite) Reduced Function: Decrease in the ability to metabolize substrate (drug and/or metabolite) ~50-70% Fully Functional: Full capability to metabolize a substrate

18 Data Presentation PopulationN (# of Subjects)Fully FunctionalLoss of Function/Greatly ReducedPMID CYP 2C9*1CYP 2C9*2CYP 2C9*3 African-American (Black) Literature Literature No Data No Data No Data No Data African (Black) Ashekenazi Jew 100No Data Caucasian 115No Data LiteratureNo Data LiteratureNo Data LiteratureNo Data Literature

19 Data Presentation 2C19 Genotype Frequency Example: 3+ Functional Alleles CYP2C19*1Caucasian: 86% African: 81% Asian: 63% Non-Functional Allele CYP2C19*2Caucasian: 13% African: 18% Asian: 30% CYP2C19*3Caucasian: 1% African: 1% Asian: 10%

20 Data Presentation Ultra Rapid Metabolizer No Data Extensive Metabolizer Caucasian: 74% African: 66% Asian: 40% Intermediate Metabolizer Caucasian: 12% African: 15% Asian: 25% Poor Metabolizer Caucasian: 2% African: 4% Asian: 16% 2C19 Phenotype Frequency Example:

21 Significant Ethnic Variations in Drug Metabolism 2D6: ~25% of all ethnic groups are intermediate metabolizers of 2D6 substrates 2C9: ~6% of Caucasians are poor metabolizers of 2C9 substrates 2C19: ~16% of Asians are 2C19 poor metabolizers 2B6: ~7-14% of African Americans are poor metabolizers of 2B6 substrates 2E1: ~30-40% Asians are 2E1 poor metabolizers

22 Thank You Everyone at Genelex!

23 References Provine, W.B "Ernst Mayr: Genetics and Speciation" Genetics 167: nder.gif&imgrefurl=http://userpages.umbc.edu/~farabaug/biol100/overheads/lect17over.html&usg=__V mqH9W1glLR4SrvgDImcgFD6czg=&h=342&w=594&sz=7&hl=en&start=3&um=1&tbnid=nlYgKs5g2ZSoi M:&tbnh=78&tbnw=135&prev=/images%3Fq%3Dfounder%2Beffect%2B- %2Bpicture%26hl%3Den%26sa%3DX%26um%3D1

24 References (2C9)

25 References (2C19)

26 References (2D6)

27 References (3A7)


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