Humans tend to categorize and classify various aspects of our lives; we arrange elements in the periodic table based on their properties and classify living beings into family, genus, and species. Nonetheless, we must acknowledge that this system of discrete classification is only sometimes feasible. Human evolution, a lengthy and intricate process, was traditionally believed to be solely determined by genetic mutations. However, as our understanding of genetics has increased, we now understand that health and well-being result from a multifaceted interplay between genetic predispositions and environmental factors. While genetic influences can render individuals more susceptible to specific illnesses, environmental exposures are crucial in determining the symptoms and severity of these conditions.
Epigenetics is the study of how behaviors and environments affect how genes work. Unlike genetic changes, epigenetic modifications are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence (What Is Epigenetics? | CDC, 2022). DNA methylation, chromatin remodeling, and non-coding RNAs (ncRNAs) are the three most investigated epigenetic modifications (Fenoglio et al., 2018). These give us insight into how various environmental factors, such as air pollution, can cause cardiovascular diseases, respiratory diseases, and cancer.
Prolonged exposure to air pollution results in cytogenetic damage (harmful alterations or abnormalities in the structure/number of chromosomes within a cell’s nucleus), DNA strand breakage, epigenetic modifications, and altered gene expression. These changes are linked to increased risk factors for various diseases, particularly cancers. It is known that breathing in air pollution harms the lungs. For example, the lung condition known as hypersensitivity pneumonitis (HP) is brought on by inhaling avian antigens and exposure to bacteria and fungi. It is most common in farmers and bird enthusiasts. It affects 5–10% of those exposed; chemical workers’ lungs are more common among those exposed to isocyanates, and farmers’ lungs are more common among those exposed to moldy hay. Bird fancier’s lung is more prevalent in people exposed to avian antigens. Genetic and epigenetic variables can be identified as responsible for variations in disease incidence. A study in India has reported that ambient air pollution is a promoting factor in the development of HP. The study demonstrates that the odds of developing HP are 7% greater for every 10 μg/m3 increase in air pollution (Mukherjee et al., 2021).
Alongside pollution, a person’s lifestyle also affects their disease susceptibility. Alzheimer’s and Early-onset dementia (EOD), defined by the onset of dementia symptoms before the age of 65, regardless of the underlying dementia syndrome, are a clear example of this. (Fenoglio et al., 2018)
In a study conducted in northern Italy (Adani et al., 2020), a broad range of environmental, occupational, and lifestyle factors for two types of EOD, Early-onset Alzheimer’s dementia (EOAD) and Early-onset frontotemporal dementia (EAOFD), were investigated. The study revealed that factors such as widow status, upper arm and head trauma, sports practice, gardening use, and occupational exposure to chemicals like fertilizers and pesticides were risk factors for early-onset dementia (EOOD). The risk was higher in middle-aged individuals, widowed, divorced, or single. The association between EOOD and EOAD was also stronger when considering occupational exposure to chemicals such as aluminum.
Moreover, Apolipoprotein E4 was identified as a risk factor for sporadic AD. Studies on humans and animals consistently show that the Apolipoprotein E (APOE) genotype affects the response to environmental risk factors in both diseases. In some cases, APOEε4 carrier status even enhances the adverse effects of environmental risk factors. Exposure to heavy metals or bad diets/lifestyles have all been reported to be worsened in APOEε4 carriers in both human and rodent studies. APOE also determines the effects of tobacco and alcohol on AD risk. Its genotype determines the direction of the impact of smoking, with smoking being detrimental to AD risk in APOEε2/3 carriers but protective in APOEε4 carriers. (Engstrom et al., 2017), (Dunn et al., 2019)Through elucidating the causes of HP, EOAD, and EOAFD, it can be stated that the intricate relationship between genetics and the environment profoundly influences human health and disease susceptibility.
Environmental factors, ranging from pollution to lifestyle choices, significantly impact health outcomes by modulating epigenetic processes. Epigenetic mechanisms serve as crucial mediators in this complex interplay, regulating gene expression without altering the DNA sequence. Understanding these interactions is essential for unraveling the underlying disease mechanisms and developing targeted interventions. Moving forward, ongoing research into the dynamic interplay between genes and the environment holds promise for advancing personalized medicine and improving public health outcomes.
Citations / References:
Fenoglio, C., Scarpini, E., Serpente, M., & Galimberti, D. (2018). Role of genetics and epigenetics in the pathogenesis of alzheimer’s disease and frontotemporal dementia. Journal of Alzheimer’s Disease, 62(3), 913–932. https://doi.org/10.3233/jad-170702
Mukherjee, S., Dasgupta, S., Mishra, P. K., & Chaudhury, K. (2021). Air pollution-induced epigenetic changes: Disease development and a possible link with hypersensitivity pneumonitis. Environmental Science and Pollution Research, 28(40), 55981–56002. https://doi.org/10.1007/s11356-021-16056-x
Adani, G., Filippini, T., Garuti, C., Malavolti, M., Vinceti, G., Zamboni, G., Tondelli, M., Galli, C., Costa, M., Vinceti, M., & Chiari, A. (2020). Environmental risk factors for early-onset alzheimer’s dementia and frontotemporal dementia: A case-control study in Northern Italy. International Journal of Environmental Research and Public Health, 17(21), 7941. https://doi.org/10.3390/ijerph17217941
Engstrom, A. K., Snyder, J. M., Maeda, N., & Xia, Z. (2017). Gene-environment interaction between lead and apolipoprotein E4 causes cognitive behavior deficits in mice. Molecular Neurodegeneration, 12(1). https://doi.org/10.1186/s13024-017-0155-2
Dunn, A. R., O’Connell, K. M. S., & Kaczorowski, C. C. (2019). Gene-by-environment interactions in alzheimer’s disease and parkinson’s disease. Neuroscience & Biobehavioral Reviews, 103, 73–80. https://doi.org/10.1016/j.neubiorev.2019.06.018
Nice work Navya