Anna Dominiczak
University of Glasgow
Professor Dame Anna Dominiczak is Regius Professor of Medicine, Vice Principal and Head of the College of Medical, Veterinary and Life Sciences at the University of Glasgow. She is one of the world’s leading cardiovascular scientists and clinical academics. Her major research interests are in hypertension, cardiovascular genomics and precision medicine, where she not only publishes extensively in top peer-reviewed journals (over 400 publications), but also excels in large-scale research funding for programmes and infrastructure (in excess of £100M over the last seven years). In 2016, she was awarded a DBE for services to cardiovascular and medical science.
Human primary or essential hypertension is a complex, polygenic trait with some 50% contribution from genes and environment. Richard Lifton and colleagues provided elegant dissection of several rare Mendelian forms of hypertension, exemplified by the glucocorticoid remediable aldosteronism and Liddle’s syndrome. These discoveries illustrate that a single gene mutation can explain the entire pathogenesis of severe, early onset hypertension as well as dictating the best treatment.
The dissection of the much more common polygenic hypertension has proven much more difficult. The real breakthrough came with the initiation of the genome wide association studies (GWAS) characterised by a much more thorough coverage of the genome with thousands single nucleotide polymorphisms (SNPs). Typically 500,000 – 2,5000,000 SNPs have been used for the big, collaborative GWAS for hypertension. These studies resulted in several “hits” or signals with a genome-wide significance and a high level of reproducibility between studies. These “hits” have been used successfully to calculate genetic risk scores for cardiovascular complications such as left ventricular hypertrophy, stroke and coronary artery disease. Intragenic signals, such as for example Uromodulin, are being used to examine new pathways for cardiovascular protection and possibly new targets for drug discovery as well as new style stratified clinical trials.
The next steps in genomic medicine belong to a combination of the next generation sequencing (NGS) and/or other “omics” data followed by linkage with electronic health records, including preferably the real time clinical data, biochemistry, imaging, histology as well as longitudinal health outcomes.
Precision medicine involves examining the genetic makeup of patients and their differing responses to drugs designed to treat specific diseases. By building up an understanding of the ‘strata’ of responses and the genetics of the diseases, we hope to create more personalised and effective forms of treatment for groups of patients most likely to benefit. Significant past investment in Scotland in electronic health records (EHRs) and translational medicine research, coupled with a vibrant healthcare technology industry, positions Scotland as the location to drive forward the precision medicine agenda globally.
Figure 1 (modified from Aronson SJ & Rehm HL, Nature 2015;526:336-342) illustrates the precision medicine ecosystem as currently implemented in very few selected centres word-wide including our own. These modalities of precision medicine are ready for the prime time now.
References:
1. Padmanabhan S, Caulfied M, Dominiczak AF. Genetic and molecular aspects of hypertension. Circ Res 2015; 116: 937-959
2. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human
hypertension. Cell 2001; 104:545-556.
3. Ehret GB, Munroe PB, Rice KM et al, Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 2011; 478:103-109.
4. WISH report. http://www.wish.org.qa/wp-content/uploads/2018/01/IMPJ4495_WISH_Precision_Medicine_Report_WEB.pdf
5. Dominiczak AF, Deles C, Padmanabhan S. Genomics and precision medicine for clinicians and scientists in hypertension. Hypertension 2017; 69: e10-e11. DOI 10.1161/HYPERTENSIONAHA.116.08252
Personalized therapies (cancer, immunology, infectious diseases, clinical case studies, et , Emerging opportunities in personalized medicine, cutting-edge new strategies and solutions
