Pharmacogenetics
Pharmacogenetics is the study of how genetic variation can lead to different responses to certain medications. Some medication may not work as effectively in some people with certain genetic changes. Some individuals may have severe reactions to their medication (called adverse drug reactions). We have been undertaking studies to see how genetic testing can be used in clinical practice to make drugs safer and more effective.
Current Projects
The Pharmacogenetics to Avoid Loss Of Hearing (PALOH) study is a project to assess a point of care genetic test to avoid hearing loss in neonates exposed to the antibiotic gentamicin. 90,000 babies every year in the UK are admitted or assessed on a neonatal intensive care unit (NICU). Most will receive the antibiotic gentamicin to protect against or treat infection. One in 500 babies have a genetic change called m.1555A>G which predisposes to complete irreversible hearing loss when given gentamicin. With colleagues at Genedrive we have developed a rapid test which can tell if babies are susceptible to this drug reaction in less than 30 minutes and so potentially save 200 babies every year in the UK from going deaf. This work, funded by the NIHR i4i program, is currently progressing well and we will trial the tests in Liverpool and Manchester from Summer 2019.
Genetics of Clopidogrel in patients with stroke. Clopidogrel is an antiplatelet drug that is widely used in the care of patients with coronary artery disease, vascular disease and stroke. 15% of individuals carry changes in a gene called CYP2C19 which mean that they do not respond to this drug. We are developing a study to look how rapid genetic tests of CYP2C19 can be employed to use drugs more effectively in the treatment of patients with stroke.
Genetics of in vitro fertilization (IVF) treatment:
A rare, but devastating, complication of IVF treatment is severe ovarian hyperstimulation syndrome (OHSS). This can in its most sever form be fatal or lead to women needing urgent treatment on intensive care. We believe that genetic factors may be important in this condition and are currently designing studies to determine the causes using whole genome sequencing approaches.
Past projects
TARGET (TPMT: Azathioprine Response to Genotyping and Enzyme Testing)
Was a randomized controlled trial to determine if genetic testing before the use of the anti-inflammatory drug azathioprine reduced the incidence of adverse drug reactions. This was the first such study conducted in the NHS funded by the Department of Health.
Our Team
MCGM Clinical & Research
Name |
Role |
Prof. William Newman |
|
Dr John McDermott |
Academic Clinical Fellow |
Dr Rachel Mahood |
Senior Research Coordinator |
St Mary’s Hospital
University of Manchester
Collaborations
Patient support groups
Research funded by
Links
References
- Cerra C, Newman WG, Tohlob D, Byers H, Horne G, Roberts SA, Mohiyiddeen L. AMH type II receptor and AMH gene polymorphisms are not associated with ovarian reserve, response, or outcomes in ovarian stimulation. J Assist Reprod Genet. 2016 Aug;33(8):1085-91. doi: 10.1007/s10815-016-0711-7. Epub 2016 May 3. PubMed PMID: 27142041; PubMed Central PMCID: PMC4974219.
- Coenen MJ, de Jong DJ, van Marrewijk CJ, Derijks LJ, Vermeulen SH, Wong DR,
Klungel OH, Verbeek AL, Hooymans PM, Peters WH, te Morsche RH, Newman WG, Scheffer H, Guchelaar HJ, Franke B; TOPIC Recruitment Team. Identification of Patients With Variants in TPMT and Dose Reduction Reduces Hematologic Events During Thiopurine Treatment of Inflammatory Bowel Disease. Gastroenterology. 2015Oct;149(4):907-17.e7. doi: 10.1053/j.gastro.2015.06.002. Epub 2015 Jun 11. PubMedPMID: 26072396.
- Thompson AJ, Newman WG, Elliott RA, Roberts SA, Tricker K, Payne K. The
cost-effectiveness of a pharmacogenetic test: a trial-based evaluation of TPMT
genotyping for azathioprine. Value Health. 2014 Jan-Feb;17(1):22-33. doi:
10.1016/j.jval.2013.10.007. PubMed PMID: 24438714.
- Province MA, Goetz MP, Brauch H, Flockhart DA, Hebert JM, Whaley R, Suman VJ, Schroth W, Winter S, Zembutsu H, Mushiroda T, Newman WG, Lee MT, Ambrosone CB, Beckmann MW, Choi JY, Dieudonné AS, Fasching PA, Ferraldeschi R, Gong L, Haschke-Becher E, Howell A, Jordan LB, Hamann U, Kiyotani K, Krippl P, Lambrechts D, Latif A, Langsenlehner U, Lorizio W, Neven P, Nguyen AT, Park BW, Purdie CA, Quinlan P, Renner W, Schmidt M, Schwab M, Shin JG, Stingl JC, Wegman P, Wingren S, Wu AH, Ziv E, Zirpoli G, Thompson AM, Jordan VC, Nakamura Y, Altman RB, Ames MM, Weinshilboum RM, Eichelbaum M, Ingle JN, Klein TE; International Tamoxifen Pharmacogenomics Consortium. CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Clin Pharmacol Ther. 2014 Feb;95(2):216-27. doi: 10.1038/clpt.2013.186. Epub 2013 Sep 23. PubMed PMID: 24060820; PubMed Central PMCID: PMC3904554.
- Newman WG. Pharmacogenetics: transforming clinical medicine. J R Coll
Physicians Edinb. 2012;42(3):244-7. doi: 10.4997/JRCPE.2012.312. Review. PubMed PMID: 22953321.
- Hadfield KD, Newman WG. Pharmacogenetics of aromatase inhibitors.
Pharmacogenomics. 2012 Apr;13(6):699-707. doi: 10.2217/pgs.12.28. Review. PubMed
PMID: 22515612.
- Newman WG, Flockhart D. Breast cancer pharmacogenomics: where we are going. Pharmacogenomics. 2012 Apr;13(6):629-31. doi: 10.2217/pgs.12.37. PubMed PMID:22515602.
- Newman WG, Murphy BF, Callard A, Payne K. A role for genetic counsellors and clinical geneticists in pharmacogenetics? Clin Genet. 2012 Aug;82(2):201-2;
author reply 203. doi: 10.1111/j.1399-0004.2012.01872.x. Epub 2012 Apr 9. PubMed PMID: 22486167.
- Callard A, Newman W, Payne K. Delivering a pharmacogenetic service: is there a role for genetic counselors? J Genet Couns. 2012 Aug;21(4):527-35. doi:
10.1007/s10897-011-9415-4. Epub 2011 Nov 4. PubMed PMID: 22052043.
- Fleeman N, Martin Saborido C, Payne K, Boland A, Dickson R, Dundar Y,
Fernández Santander A, Howell S, Newman W, Oyee J, Walley T. The clinical
effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review. Health Technol Assess. 2011 Sep;15(33):1-102. doi: 10.3310/hta15330. Review. PubMed PMID: 21906462; PubMed Central PMCID: PMC4780889.
- Newman WG, Payne K, Tricker K, Roberts SA, Fargher E, Pushpakom S, Alder JE, Sidgwick GP, Payne D, Elliott RA, Heise M, Elles R, Ramsden SC, Andrews J,
Houston JB, Qasim F, Shaffer J, Griffiths CE, Ray DW, Bruce I, Ollier WE; TARGET
study recruitment team. A pragmatic randomized controlled trial of thiopurine
methyltransferase genotyping prior to azathioprine treatment: the TARGET study. Pharmacogenomics. 2011 Jun;12(6):815-26. doi: 10.2217/pgs.11.32. Epub 2011 May 3. PubMed PMID: 21692613.
- Payne K, Fargher EA, Roberts SA, Tricker K, Elliott RA, Ratcliffe J, Newman
WG. Valuing pharmacogenetic testing services: a comparison of patients’ and
health care professionals’ preferences. Value Health. 2011 Jan;14(1):121-34. doi:
10.1016/j.jval.2010.10.007. PubMed PMID: 21211494.
- Ferraldeschi R, Newman WG. Pharmacogenetics and pharmacogenomics: a clinical
reality. Ann Clin Biochem. 2011 Sep;48(Pt 5):410-7. doi: 10.1258/acb.2011.011084.
Epub 2011 Jul 6. Review. PubMed PMID: 21733927.
- Higgs JE, Payne K, Roberts C, Newman WG. Are patients with intermediate TPMT
activity at increased risk of myelosuppression when taking thiopurine
medications? Pharmacogenomics. 2010 Feb;11(2):177-88. doi: 10.2217/pgs.09.155.
Review. PubMed PMID: 20136357.