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Pharmacogenetics of healthy volunteers in Puerto Rico

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Published/Copyright: October 24, 2015
Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 30 Issue 4

Abstract

Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer’s disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island.

Keywords: genetic polymorphisms; genotyping; healthy volunteers; personalized medicine; pharmacogenetics; Puerto Ricans
Corresponding author: Jorge Duconge, Pharmaceutical Sciences Department, School of Pharmacy, University of Puerto Rico, Medical Sciences Campus (UPR-MSC), 3rd Floor, Room 325-14, Pharmacy Building, P.O. Box 365067, San Juan, Puerto Rico 00936-5067, Phone: +(787) 758 2525 ext. 5312, Fax: +(787) 767-2796, E-mail:

Acknowledgments

We thank the Laboratory of Personalized Medicine, Hartford, CT, and the UPR-MSC Research Center in Minority Institutions Center for Genomics in Health Disparities and Rare Disorders for their support and for providing the resources and facilities for performing genetic assays. The authors also want to thank Mohan Kocherla, MSc; Krystyna Gorowski, MSc; Myrna E. Casillas, PharmD; Sonia E. Rodríguez, PharmD; and Jennifer Serrano, PharmD, for their help in the genotyping tests and data analysis.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This review was supported in part by the National Heart, Lung, and Blood Institute grant number SC1 HL123911, the Research Center in Minority Institutions award number 8G12 MD007600 from the National Institute on Minority Health and Health Disparities, and the Minority Biomedical Research Support-Research Initiative for Scientific Enhancement at the University of Puerto Rico, Medical Sciences Campus, grant number R25GM061838. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the United States Government. Authors have no relevant affiliation or financial involvement with any organization or entity with a financial interest in or conflicts of interest with the subject matter or materials discussed in the article that need to be disclosed. No writing assistance was utilized in the production of this manuscript.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. United States Census Bureau. About Hispanic Origin. Hispanic Origin. 2013 [Internet]. Available at: http://www.census.gov/topics/population/hispanic-origin/about.html (accessed 2015 Sep 20).Search in Google Scholar

2. Bryc K, Velez C, Karafet T, Moreno-Estrada A, Reynolds A, Auton A, et al. Colloquium paper: genome-wide patterns of population structure and admixture among Hispanic/Latino populations. Proc Natl Acad Sci USA 2010;107(Suppl 2): 8954–61.10.1073/pnas.0914618107Search in Google Scholar PubMed PubMed Central

3. Claudio-Campos K, Duconge J, Cadilla CL, Ruaño G. Pharmacogenetics of drug metabolizing enzymes in U.S. Hispanics. Drug Metabol Drug Interact 2015;30:87–105.10.1515/dmdi-2014-0023Search in Google Scholar

4. Division de Prevencion y Control de Enfermedades Cronicas. Secretaria Auxiliar para la Promocion de la Salud. Plan de accion de enfermedades cronicas para Puerto Rico 2014–2020. 2014.Search in Google Scholar

5. Cespedes-Garro C, Naranjo M, Ramirez R, Serrano V, Fariñas H, Barrantes H, et al. Pharmacogenetics in Central American healthy volunteers: interethnic variability. Drug Metab Perspect Ther 2015;30:19–31.10.1515/dmdi-2014-0025Search in Google Scholar PubMed

6. Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement (Chinese edition). J Chin Integr Med 2009;7:889–96.10.3736/jcim20090918Search in Google Scholar

7. Food and Drug Administration. Drugs Table of Pharmacogenomic Biomarkers in Drug Labeling. 2014 [Internet]. Available at: http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm.Search in Google Scholar

8. PharmGKB. CPIC Gene-Drug Pairs [Internet]. Available at: https://www.pharmgkb.org/page/cpic (accessed 2015 Jun 7).Search in Google Scholar

9. Amigo J, Salas A, Phillips C, Carracedo A. SPSmart: adapting population based SNP genotype databases for fast and comprehensive web access. BMC Bioinform 2008;9:428.10.1186/1471-2105-9-428Search in Google Scholar PubMed PubMed Central

10. Green SA, Turki J, Innis M, Liggett SB. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 1994;33:9414–9.10.1021/bi00198a006Search in Google Scholar PubMed

11. Choudhry S, Ung N, Avila PC, Ziv E, Nazario S, Casal J, et al. Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. Am J Respir Crit Care Med 2005;171:563–70.10.1164/rccm.200409-1286OCSearch in Google Scholar PubMed

12. Catena C, Colussi G, Nait F, Capobianco F, Sechi L. Elevated homocysteine levels are associated with the metabolic syndrome and cardiovascular events in hypertensive patients. Am J Hypertens 2015;28:943–50.10.1093/ajh/hpu248Search in Google Scholar PubMed

13. Ansari R, Mahta A, Mallack E, Luoa JJ. Hyperhomocysteinemia and neurologic disorders: a review. J Clin Neurol 2014;10:281–8.10.3988/jcn.2014.10.4.281Search in Google Scholar PubMed PubMed Central

14. Zhu S, Li J, Bing Y, Yan W, Zhu Y, Xia B, et al. Diet induced hyperhomocysteinemia increases intestinal inflammation in an animal model of colitis. J Crohns Colitis 2015;9:708–19.10.1093/ecco-jcc/jjv094Search in Google Scholar PubMed

15. Etienne-Grimaldi M-C, Francoual M, Formento J-L, Milano G. Methylenetetrahydrofolate reductase (MTHFR) variants and fluorouracil-based treatments in colorectal cancer. Pharmacogenomics 2007;8:1561–6.10.2217/14622416.8.11.1561Search in Google Scholar PubMed

16. Yang L, Hu X, Xu L. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis. Tumor Biol 2012;33:1445–54.10.1007/s13277-012-0395-2Search in Google Scholar

17. Garcia-Fragoso L, Garcia-Garcia I, Leavitt G, Renta JY, Ayala M, Cadilla CL. MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers. Int J Genet Mol Biol 2010;2:43–7.Search in Google Scholar

18. Ayala-Rivera M. Methylenetetrahydrofolate reductase, MTHFR, gene mutations in the Puerto Rican population (Ph.D. thesis). June 1999. Retrieved from the University of Puerto Rico Medical Sciences Campus library. Vol. 1, pp. 26–43.10.1097/00125817-199901000-00123Search in Google Scholar

19. Whirl-Carrillo M, McDonagh E, Hebert J, Gong L, Sangkuhl K, Thorn CF, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 2012;92:414–7.10.1038/clpt.2012.96Search in Google Scholar

20. Yuan H-Y, Chen J-J, Lee MT, Wung J-C, Chen Y-F, Charng M-J, et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet 2005;14:1745–51.10.1093/hmg/ddi180Search in Google Scholar

21. Schwarz UI, Stein CM. Genetic determinants of dose and clinical outcomes in patients receiving oral anticoagulants. Clin Pharmacol Ther 2006;80:7–12.10.1016/j.clpt.2006.04.008Search in Google Scholar

22. Duconge J, Cadilla C, Windemuth A, Kocherla M, Gorowski K, Seip RL, et al. Prevalence of combinatorial CYP2C9 and VKORC1 genotypes in Puerto Ricans: implications for warfarin management in Hispanics. Ethn Dis 2009;19:390–5.Search in Google Scholar

23. Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 2013;138:103–41.10.1016/j.pharmthera.2012.12.007Search in Google Scholar

24. Crespi C, Miller V. The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH: cytochrome P450 oxidoreductase. Pharmacogenetics 1997;7:203–10.10.1097/00008571-199706000-00005Search in Google Scholar

25. Human Cytochrome P450 (CYP) Allele Nomenclature Committee. The human cytochrome P450 (CYP) allele nomenclature database [Internet]. Available at: http://www.cypalleles.ki.se/index.htm.Search in Google Scholar

26. Rettie AE, Wienkers LC, Gonzalez FJ, Trager WF, Korzekwa KR. Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharma 1994;4:39–42.10.1097/00008571-199402000-00005Search in Google Scholar

27. Steward DJ, Haining RL, Henne KR, Davis G, Rushmore TH, Trager WF, et al. Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics 1997;7:361–7.10.1097/00008571-199710000-00004Search in Google Scholar

28. Scott SA, Jaremko M, Lubitz SA, Kornreich R, Halperin JL, Desnick RJ. CYP2C9*8 is prevalent among African Americans: implications for pharmacogenetic dosing. Pharmacogenomics 2009;10:1243–55.10.2217/pgs.09.71Search in Google Scholar

29. Xie H-G, Prasad HC, Kim RB, Stein CM. CYP2C9 allelic variants: ethnic distribution and functional significance. Adv Drug Deliv Rev 2002;54:1257–70.10.1016/S0169-409X(02)00076-5Search in Google Scholar

30. Kidd R, Curry T, Gallagher S. Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics 2001;11:803–8.10.1097/00008571-200112000-00008Search in Google Scholar PubMed

31. Luo H-R, Poland RE, Lin K-M, Wan Y-JY. Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study. Clin Pharmacol Ther 2006;80:33–40.10.1016/j.clpt.2006.03.003Search in Google Scholar PubMed

32. Orengo-Mercado C, Nieves B, López L, Vallés-Ortiz N, Renta JY, Santiago-Borrero PJ, et al. Frequencies of functional polymorphisms in three pharmacokinetic genes of clinical interest within the admixed Puerto Rican population. J Pharmacogenomics Pharmacoproteomics 2013;4:1–6.10.4172/2153-0645.1000113Search in Google Scholar PubMed PubMed Central

33. Duconge J, Cadilla CL, Renta JY, Silen-Rivera P, Piovanetti P, Garcia-Berdecia R, et al. Prevalence of CYP2C19 gene polymorphisms in the Puerto Rican population: a preliminary report. P R Health Sci J 2008;27:2–3.Search in Google Scholar

34. Duconge J, Escalera O, Korchela M, Ruaño G. Clinical implications of genetic admixture in Hispanic Puerto Ricans: impact on the pharmacogenetics of CYP2C19 and PON1. In: Sanodou D, editor. Clinical Applications of Pharmacogenetics. Rijeka: InTech, 2012:151–63.10.5772/28567Search in Google Scholar

35. Bijl MJ, van Schaik RH, Lammers L, Hofman A, Vulto AG, van Gelder T, et al. The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users. Breast Cancer Res Treat 2009;118:125–30.10.1007/s10549-008-0272-2Search in Google Scholar PubMed

36. Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. More codeine fatalities after tonsillectomy in North American children. Pediatrics 2012;129:e1343–7.10.1542/peds.2011-2538Search in Google Scholar PubMed

37. Sachse C, Brockmöller J, Bauer S, Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 1997;60:284–95.Search in Google Scholar

38. Leathart JB, London SJ, Steward A, Adams JD, Idle JR, Daly AK. CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in Los Angeles. Pharmacogenetics 1998;8:529–41.10.1097/00008571-199812000-00010Search in Google Scholar PubMed

39. Roh HK, Dahl ML, Johansson I, Ingelman-Sundberg M, Cha YN, Bertilsson L. Debrisoquine and S-mephenytoin hydroxylation phenotypes and genotypes in a Korean population. Pharmacogenetics 1996;6:441–7.10.1097/00008571-199610000-00008Search in Google Scholar PubMed

40. Yoon YR, Cha IJ, Shon JH, Kim KA, Cha YN, Jang IJ, et al. Relationship of paroxetine disposition to metoprolol metabolic ratio and CYP2D6*10 genotype of Korean subjects. Clin Pharmacol Ther 2000;67:567–76.10.1067/mcp.2000.106128Search in Google Scholar PubMed

41. Gaedigk A, Gotschall RR, Forbes NS, Simon SD, Kearns GL, Leeder JS. Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data. Pharmacogenetics 1999;9:669–82.10.1097/01213011-199912000-00002Search in Google Scholar PubMed

42. Johansson I, Oscarson M, Yue Q. Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol 1994;46:452–9.10.1016/S0026-895X(25)09721-4Search in Google Scholar

43. Gaedigk A, Isidoro-García M, Pearce RE, Sánchez S, García-Solaesa V, Lorenzo-Romo C, et al. Discovery of the nonfunctional CYP2D6 31 allele in Spanish, Puerto Rican, and US Hispanic populations. Eur J Clin Pharmacol 2010;66:859–64.10.1007/s00228-010-0831-4Search in Google Scholar PubMed

44. González-Tejera G, Gaedigk A, Corey S. Genetic variants of the drug-metabolizing enzyme CYP2D6 in Puerto Rican psychiatry patients: a preliminary report and potential implications for breast cancer patients. P R Health Sci J 2010;29:299–304.Search in Google Scholar

45. Mackness M, Mackness B. Paraoxonase 1 and atherosclerosis: is the gene or the protein more important? Free Radic Biol Med 2004;37:1317–23.10.1016/j.freeradbiomed.2004.07.034Search in Google Scholar PubMed

46. Bouman H, Schömig E, van Werkum JW, Velder J, Hackeng CM, Hirschhäuser C, et al. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med 2011;17:110–6.10.1038/nm.2281Search in Google Scholar PubMed

47. Holmes MV, Shah T, Vickery C, Smeeth L, Hingorani AD, Casas JP. Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies. PLoS One 2009;4:e7960.10.1371/journal.pone.0007960Search in Google Scholar PubMed PubMed Central

48. Cavallari LH, Vaynshteyn D, Freeman K, Wang D, Perera M, Takahashi H, et al. CYP2C9 promoter region single-nucleotide polymorphisms linked to the R150H polymorphism are functional suggesting their role in CYP2C9*8-mediated effects. Pharmacogenet Genom 2013;23:228–31.10.1097/FPC.0b013e32835e95c7Search in Google Scholar PubMed PubMed Central

49. Renta JY, Cadilla CL, Vega ME, Hillyer GV, Estrada C, Jiménez E, et al. Longitudinal studies on maternal HIV-1 variants by biological phenotyping, sequence analysis and viral load. Cell Mol Biol (Noisy-le-grand) 1997;43:1097–114.Search in Google Scholar

50. Mahadeo KM, Diop-Bove N, Ramirez SI, Cadilla CL, Rivera E, Martin M, et al. Prevalence of a loss-of-function mutation in the proton-coupled folate transporter gene (PCFT-SLC46A1) causing hereditary folate malabsorption in Puerto Rico. J Pediatr 2011;159:623–7.10.1016/j.jpeds.2011.03.005Search in Google Scholar PubMed PubMed Central

51. Santiago Borrero PJ, Rodríguez-Pérez Y, Renta JY, Izquierdo NJ, Del Fierro L, Muñoz D, et al. Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak syndrome type 1 and 3 mutations in Puerto Rico. J Invest Dermatol 2006;126:85–90.10.1038/sj.jid.5700034Search in Google Scholar PubMed PubMed Central

52. Cordova A, Barrios NJ, Ortiz I, Rivera E, Cadilla C, Santiago-Borrero PJ. Poor response to desmopressin acetate (DDAVP) in children with Hermansky-Pudlak syndrome. Pediatr Blood Cancer 2005;44:51–4.10.1002/pbc.20210Search in Google Scholar PubMed

Received: 2015-7-1
Accepted: 2015-9-24
Published Online: 2015-10-24
Published in Print: 2015-12-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Clinical pharmacy service practice in a Chinese tertiary hospital
  4. Reviews in Population Pharmacogenomics
  5. CYP2D6 in Amerindians from Southern Mexico: low variability and higher frequency of functional alleles
  6. Pharmacogenetics of healthy volunteers in Puerto Rico
  7. Original Articles
  8. ABCG2/BCRP interaction with the sea grass Thalassia testudinum
  9. Effect of rifampicin pretreatment on the oral bioavailability of domperidone in healthy human volunteers
  10. Efficacy of subgingivally delivered atorvastatin and simvastatin as an adjunct to scaling and root planing
  11. Case Report
  12. Fluvoxamine-associated oscillopsia and a role for personalized medication dosing
  13. Acknowledgment
https://doi.org/10.1515/dmpt-2015-0021
Keywords for this article
genetic polymorphisms; genotyping; healthy volunteers; personalized medicine; pharmacogenetics; Puerto Ricans

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Clinical pharmacy service practice in a Chinese tertiary hospital
  4. Reviews in Population Pharmacogenomics
  5. CYP2D6 in Amerindians from Southern Mexico: low variability and higher frequency of functional alleles
  6. Pharmacogenetics of healthy volunteers in Puerto Rico
  7. Original Articles
  8. ABCG2/BCRP interaction with the sea grass Thalassia testudinum
  9. Effect of rifampicin pretreatment on the oral bioavailability of domperidone in healthy human volunteers
  10. Efficacy of subgingivally delivered atorvastatin and simvastatin as an adjunct to scaling and root planing
  11. Case Report
  12. Fluvoxamine-associated oscillopsia and a role for personalized medication dosing
  13. Acknowledgment
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