Dr Pankaj Mankad writes on genomics and its role in disease prediction and prevention
Genomics, the interactive science of genes and environmental influence, is progressing since the discovery of complete Human Genome (Human Genome Project, 2003). Moving on from a single gene — single disease Mendelian principles (Gregor Mendel, 1822-1884), several chronic diseases including cancer are now proven to be related to Single Nucleotide Polymorphism (SNP) in a gene. Each gene/DNA has four nucleotide bases and they must remain in pairs to help form proteins for body functions. There are millions of these bases in a gene. They always have their fixed locations. SNP is only a subtle change in the single nucleotide base combination in a gene!
Not all SNPs are harmful but most problems arise because of SNPs and other gene abnormalities. A particular SNP may either increase or even reduce the risk of developing a disease. Genomic assessment, for this purpose, is usually done from one’s saliva or a buccal swab sample (saliva is preferable) to identify relevant SNPs with a propensity to increase a disease risk. Almost invariably for every chronic disease a large number of SNPs play a contributory role, of a variable proportion, for disease propensity. Once a person’s genome assessment is done statistical association is made, of every relevant SNP found with many important common diseases, to derive one’s relative risk of developing a disease. These data, if combined with personal data (family history, habits, life style etc), would create a robust disease risk prediction ability for an individual.
Common chronic diseases that could be predicted with this approach. Periodic health checks are fast becoming an established entity in India. These health checks can help early detection of a disease, but their role in disease prevention is limited. Knowing one’s own risk of a particular disease would empower a person to take a focussed and committed approach to appropriate lifestyle modifications.
How is it possible that despite I have ‘bad’ genes, I could prevent a diseaseIJ like a light switch, genes could also be turned ‘on’ or ‘off’. Turned off genes can’t cause damage as they are unable to guide manufacture of abnormal disease specific protein. In order for a disease to develop, the genes must be expressed in abnormal proteins. Gene expression is governed by the cellular material — the epigenome — that sits on top of the genome. It is through these epigenetic marks that environmental factors like diet, stress, exercise, prenatal nutrition etc can make an imprint on genes; causing bad habits to turn genes ‘on’ and good habits turning them ‘off’. This trait may pass on from one generation to the next.
Prevention advice, in many instances, is individualised based on genetic assessment of nutrition and metabolic profile and even exercise response genetic makeup of a person. This is just the beginning of an exciting field of personalised medicine, moving forward from (genetic) ‘base pairs to bed side.’ let us examine some real life scenarios.
Heart disease is not simply a condition caused by excess fat and cholesterol. There are many other modifiable risk factors, some genetically influenced, which can predispose a person to a heart disease.For example, many people, as high as 40 per cent in some studies, have a genetic inability to properly metabolise folic acid in the body (MTHFR gene). This can lead to a build-up of homocysteine in the bloodstream, causing increased risk of blood clots and atherosclerosis. For a person with this genetic variation, the only way to reduce risk is to take the active form of folic acid, which is not found in common vitamin supplements. Thus genomics-enabled medical technology can run various what-if scenarios and combine related genetic data to disease risk and show whether diet, exercise, medication, or some other factor or combination of factors has the greatest statistical likelihood of reducing
that risk. It is important to bear in mind that most cancers are neither inherited nor have genetic basis. Environmental factors play a major role in cancer. Genomics has also a great deal to offer in individualising drug treatment (Pharmaco-genomics).
(The writer is director and physician at XCode life Sciences)