Monika Kumar

 Genetic Determinants of Health  Definition (what) Genetics is the science that deals with the study of genes and heredity. It imparts information about traits and qualities passed from parents to the offspring. Genes are composed of the basic building block, the DNA, which is loaded with complete information about the working of the body. Any change in a single base of the double-helix DNA sequence results in genetic modification. Genes of an individual thus, determine the health and well-being of the individual by controlling the pathophysiology and metabolism of the body. DNA and hence the genes are stored in the form of chromosomes. Humans have 23 pairs of chromosomes inside the nucleus of each cell of the body and play role in diverse life processes such as growth and development, metabolism, physiology, process of aging as well as pathology. Modifications in genes prevent them from performing normal functions; which are responsible for inappropriate formation of proteins and thus, normal functioning is altered. Moreover, genetic modifications influence the response of individual towards medicines, allergies, tastes, likes and dislikes as well as vulnerability to diseases. Variations in genes are indicators why some individuals are more prone to diseases and others are not, why some people show signs of aging and premature greying of hair while others do not and also why population of a particular place remains healthier and show resistance to disease while other segment of population displays sign of vulnerability. Thus, genes of individuals play the most imperative part in determining health and well-being (Genetics, n.d.). a. Scope Genetic determinants of health are vital to comprehend in the present epoch. Every aspect of life is determined through the universal molecule, the DNA, which bears common ancestry and present as the genetic material in all life forms except for a few viruses. Genes are preserved over millions of years and did not change with evolution. Human genome and also genome of various model organisms are being explored and similarities are found in genes of living organisms. Scientists study genes of other animals and compare the genomes of other species to unearth resemblances and differences in order to enhance an understanding regarding how genes function and control the life processes. Therefore, animal models are used to study the gene expression and the role played by genes in physiological and metabolic process of life and then their functions could be correlated with humans (Genetics, n.d.). This holds a wider aspect as each and every activity inside the body and also the phenotypic characters as well as behavior of the person all guided by the genes.This aids in developing novel strategies to cure and prevent human diseases. Moreover, research is also carried out to know the genes responsible for causing pathogenicity and to treat the infections caused by fungus, bacteria and viruses. Microbes also influence body and health and to make the best use of microbes and other life-forms for the betterment of human survival. The present study is an attempt to understand the role played by genetic determinants in the health and well-being of the population. b. Occurrence Genetics play vital role in the existence of life. With the completion of genome project, new domains of exploration are opening everyday and genetics is finding its way in wide range of products comprising medicine, agriculture, food items, organogenesis, and animal modifications to human modifications. Paradigm like advanced therapy medicinal products (ATMPs) encompassing gene therapy, which besides altering genes of the organism also modifies the characteristics of life-forms (Goula et al., 2020), indicating that genetics is not confined to laboratories but it is dissemination for the use of common people. Genes determine the condition of well-being, therefore designated as determinants of health. The interrelationships between genes determine the health of individual and in turn, health of the population. Genetic determinants encompass- sex of the individual, aging, diseases (both genetic ailments as well as pathological conditions) etc. By manipulating genes, novel organisms are being created, designated as GMOs (Genetically Modified Organisms) where mutation is induced by chemical, radiation, transgenesis and by transposons. Knock out genes and vectors are created to play role in gene manipulation and to understand the role of gene in determining health and what role do they play in the health of people (Model Organisms., 2018). By studying different aspects of genetics using model organisms, environmental factors contributing to the modifications by interacting with the genes determine the wellness of the individual. For instance, aging and longevity depends on genetic determinants. At younger age, numerous environmental factors infectious diseases, trauma and rare conditions cause death. As the person grows old, cancer and cardiovascular diseases appear in middle age. At age of >70 years, various polygenic components play role and longevity genes predominates the environmental impact in determination of lifespan (Moris et al., 2019). Genetics influence the physical and cognitive capabilities and these abilities decline with age owing to poor cellular coordination. Aging and impact of a few diseases also depends on the environment of the place, living styles, eating habits and also the ancestry. For instance, individuals belonging to Africa, South Asia, Central and South America and Middle East are genetically predisposed to sickle cell anaemia. Genetics play important role in conditions like cancer where gene modification results in uncontrolled proliferation of cells leading to the formation of tumour and eventually, if the condition is not treated, it may result in death of the organism. Triggering of protooncogenes in many cases is also found to have hereditary links. Besides cancer, aging, haemophilia, and cystic fibrosis are also predefined by genes (Moris et al., 2019), indicating that the common and prevalent diseases have genetic links. c. Impact, consequences, public health significance Modification in genetic determinants of health i.e. genes, brings devastating consequences. Gene therapy has influenced health modifications to a greater extent and thereby aids in treatment of many diseases. Gene therapy involves genetic modification of the gene, replacing the defective gene with the functional one. The method involves injection of the gene into the defective cell such as cancer cell to catalyse destruction of the cell and revert it to the normal cell. Gene therapies also involve the stimulation of gene to produce protein molecules, insert viral or bacterial DNA in the form of vaccine, and promote tissue growth by replacing the defective gene with the healthy gene. Promote the process of repair of damaged cells in the tissue. Thus, gene manipulation in the form of gene therapy has greater impact on the well-being of the individual. For a common person, the message is conveyed that gene therapy might be helpful in treating various genetic diseases. The process provides job opportunities for those working in this field. However, gene therapy may impose negative consequences as well, when the products which are not as per the requirements are thrown out in the environment, they might become deleterious to the environment and another cleaning process needs to be implemented to clear the toxic waste. However, if the therapy is not checked properly, the toxic product(s) may be fatal to the individual. Also, the cost of the gene therapy is very high and only wealthy people are able to afford it (Linda, n.d). 2. Determinants The genetic determinants of health encompass various marker genes that act as the indicator for ailment, for instance increase in the level of C-Reactive Protein (CRP) may be the sign of aging in a similar manner high level of alpha-faeto protein (AFP) in the body could be the indicator of cancer. For a common man, AFP test value carries a meaning that they are safe or carrying cancer. However, it is imperative to understand that genetic determinants define the health of common man and safeguard them from various ailments by pre-informing them. a. Evidence The intricate aging process is categorized by modulation of chief cellular processes, which is evident in nine characteristic features of aging encompassing telomere attrition, genomic instability, altered intercellular communication, stem-cell exhaustion, cellular senescence, mitochondrial dysfunction, deregulated nutrient sensing and epigenetic alterations. These cellular changes are responsible for age-dependent modifications in organs and tissues. Changes are also reported in hematopoietic cells and also in corresponding stromal cells in the microenvironment of the bone marrow and other immunocompetent cells which alter the immunoregulatory interactions and inflammation. These features are responsible for anaemia as well as augmentation in the level of C-reactive proteins; the cellular characteristics are responsible for enhanced cardiovascular mortality (Bruserud et al., 2022). The information is vital for healthcare providers to safeguard public health in more scientific manner. 3. Interventions (with evidence) Evidently, lifestyle components and environmental factors are imperative for young individuals but genomic changes affect cellular functions and resistance to stress in a more profound manner. Researches involving genome-wide lessons implicate ~57 gene loci in a lifespan of an individual. Dysregulation of chromatin network or the transcriptional functions play vital role in aging. Bioinformatic analysis reveals the involvement of diverse interactive networks, which distinguishes between the functioning of young cells and the old cells. When the young cell replicates into senescence, a drift is observed in exceedingly regulating chromatin marks between repressed and active cells and in the process, the inactive genes leak leading to the breakdown in chromatin connectivity and insulators and associated domains become weak. Consequently, the constitutive heterochromatin gives room to the senescence-linked heterochromatin foci; this is responsible for the process of aging (Morris et al., 2019). a. Prevention No biological procedures are known to be free of genetic contribution, i.e. all the biological processes are dependent on genetics. Longevity could be attained by caloric restriction (CR) as well as traditional healthy diet intake. CR delays aging and amends aging-related diseases, it is essential to prevent people from natural and synthetic compounds that are known to mimic the outcomes of CR (Morris et al., 2019). This is again imperative as it involves a public awakening towards healthy lifestyle. b. Services Health care systems across the globe are yet in the primitive stage of application cell and gene therapy in the clinical settings. In 2001, South Korea authorized the first cell therapy product while in 2003 China came with first gene therapy product. Noteworthy to highlight that only 48 new gene therapy and cell therapy products got authorized by the end of 2018. Cell and gene therapy products were high priced in health care system. Moreover, limited evidence about the safety of these products raised concern on the efficacy of such therapies and this emerged as a barrier to reimburse the cost by public as well as private buyers. Considering the services provided by these technologies and their hazardous implications, four cell and gene therapy products were withdrawn form the EU market (Shukla et al., 2020). These services are devised for the betterment of the people however, if the technology is not foolproof and are imposing deleterious consequences, and then it cannot be accepted in public domain. Considering the risk imposed by the cell and gene therapy regenerative medicine garnished the health industry. Regenerative medicine potentiates the generation of new as well as integrated cognitive field. The field demands systematic research and inputs in the form of knowledge to provide innovation and best practices in the field of Advanced Therapy Medicinal Products (ATMPs). This deals with diseases where traditional medicines are ineffective (Goula et al., 2020). c. Biomedical Interventions This deals with the nutrition or the diet intervention so as to amend any kind of health imbalance. This imbalance could be related to immune system, oxidative stress, and gut health or nutrition deficiency. Dietary components encompassing green tea, sprouts, broccoli and soyabean are emerging as bioactive compounds that prevent aging. Resveratrol, which is sirtuin 1 activator promote healthy aging and enhance longevity. Antidiabetic drug metformin, senolytics, synthetic sirtuin-activating compounds also delay aging process. Long-term intake of epigenetic diet alters chromatin profiles and delay aging process as well as diminishes risk of degenerative aging caused by cancer, type 2 diabetes, cardiovascular disease as well as neurodegenerative disabilities (Morris et al., 2019). 4. Current efforts Genetics play vital role in enhancing the understanding about the gene expression, both in case of disease and well-being genes are always expressed as long as life persists. In the present scenario where Covid-19 pandemic has shown the world that genetic manipulation can bring devastating consequences and that infection with the virus can potentially alter the genetic make-up of a person, it is evident that genetic interaction could be devastating (Thapliyal et al., 2022). a. Global/ Local From local markets to global markets, genetics has shown its importance to every human in the past two years. Health and life is solely attributed to the wonders and disasters brought by gene manipulation and gene products. Wonders came in the form of vaccine for the Covid-19 Corona virus infection, which were then distributed across the world to overcome the situation of pandemic. The vaccines were marketed globally to combat the disease. Local pharmaceutical companies came forward to manufacture the vaccine to meet the rising demand of the vaccine and with their efforts the world could survive three waves of corona virus infection. However, the virus was potentially strong enough to cause mortality in some individuals and some part of the world displayed higher rate of mortality (e.g. the USA, Brazil and UK) while rate of mortality was less in most of the Eastern nations. Indicating that besides the health facilities individuals could not resist the corona virus infection and therefore their genetic makeup easily got modified by the virus, thereby disturbing their biochemical pathways. Thus, eating habits, lifestyles could be the determining factors to make the genes more vulnerable. However, not much could be assessed till date and it is a long way to understand the genetics behind susceptibility to infection. Corona virus infection paved the way for general population to understand that healthy lifestyle and hygiene could serve as a genetic determinant of the better health outcomes and thus, people understood that they can take care of themselves if they follow simple rules of health and hygiene. 5. Challenges The current pandemic has brought a challenge for the human race; many lost their lives and displayed diverse modifications in their biochemical pathways. Research has taken a new path in portraying genetic determinants of health away from aging and other aspects, as determinants of ageing and diseases are now less interesting since Covid-19 has smashed everything and has altered cellular and biochemical cycles which is a matter of great concern. 6. Priorities & Policy Priorities and policies changed after Covid-19 pandemic as health policies need to be reframed and world need to be prepared for more such interventions in the present era of gene manipulation. Any intentional/ unintentional exploration could be devastating. Policies at the local, state and federal levels influence people and population health. For instance, imposing fine for not wearing mask could generate awareness and safeguard people from combating diseases especially cold and corona infection. Such policies influence entire population over a given interval, while at the same time they aid in changing the behaviour of individuals as well (Determinants of health, 2020). 7. Recommendations a. Key indicators and monitoring It is imperative to understand the genetic determinants of health from a new perspective, especially when infections are taking an undefined pattern and imposing challenges in front of the mankind and all the more to the healthcare professionals. Healthcare team at every corner of the world needs to be on watch and any novel symptom should to be immediately reported. Monitoring has therefore become highly crucial and it is not only the responsibility of physicians but now it is the responsibility of every mankind to safeguard humanity. Poor health outcomes could be attributed to the incompetent and obsolete health policies and this may result in poor access to health services and with compromised quality. It is therefore recommended that health services- 1. Should incorporate health insurances 2. Should be cost effective 3. Language access 4. Easily available 5. Policy for unmet health requirements 6. No delay in receiving appropriate care 7. Should provide preventive services 8. Preventing hospitalizations if not necessary 9. Promoting healthy eating 10. Promoting hygienic lifestyle 11. Encouraging people to quit substance use and smoking (Determinants of health, 2020). References Bruserud, O., Vo, A. K., Rekvam, H. (2022). Hematopoiesis, Inflammation and Aging- The Biological Background and Clinical Impact of Anaemia and Increased C-Reactive Protein Levels on Elderly Individuals. J. Clin. Med. 11(706), 2-35. Determinants of Health. (2020). Retrieved from http://www.healthypeople.gov/2020/about/foundation-health-measures/Determinants-of-Health. Genetics. (n.d.). What is genetics? Retrieved from https://www.nigms.nih.gov/education/fact-sheets/Pages/genetics.aspx. Goula, A., Gkioka, V., Michalopoulos, E., Katsimpoulas, M., Noutsias, M. et al. (2020). Advanced Therapy Medicinal Products Challenges and Perspectives in Regenerative Medicine. J Clin Med Res. 12(12), 780-786. Linda, Li. (n.d.). Human Gene Therapy. Retrieved from Human Gene Therapy - Gene Therapy (weebly.com) Model Organisms (2018). Retrieved from Model Organisms | NIH Center for Scientific Review. Morris, B. J., Willcox, B. J., Donlon, T. A. (2019). Genetic and epigenetic regulation of human aging and longevity. BiochemBiophys Acta Mol Basis Dis. 1865(7),-. Shukla, V., Seoane-Vazquez, E., Fawaz, S., Brown, L.M., Rodriguez-Monguio, R. (2020). The landscape of cellular and gene therapy products: Cost, approvals, and discontinuations. Hum Gene Ther Clin Dev. 30(3), 102-113. Thapliyal, J., Bhattacharyya, M., Prakash, S., Patni, B., Gautam, S. and Gautam, A. S. (2022). Addressing the relevance of COVID-19 pandemic in nature and human socio-economic fate. Stoch Environ Res Risk Assess. 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