Global Health Equity Foundation, GHEF

Aberrant Epigenomic Modulations in Global Health Outcomes, Optimization and Improvement

Currently, racial/ethnic minorities health outcomes remain a substantial explanation of the USA ranking low with respect to global health outcomes. Specifically of all the industrialized nations in the world, US ranks low with respect to infant mortality, maternal mortality and life expectancy. The observed marginalized outcomes in the USA, comparing Japan, Italy, Scandinavians, etc. requires our understanding of how environment related to racial/ethnic minorities predispose to disease incidence, morbidity, impaired prognosis, excess mortality and survival disadvantage, except Asian and Pacific islanders, with the best outcome of health, relative to their white counterparts except the underserved whites.

While health remains not a mere absence of a physical disease process, but a complete and total state of social, economic and mental well-being. Public health reflects what we as a society could do to remain healthy. With the specific goal of public health and clinical medicine, the understanding of disease risk determinants, prognosis, survival and mortality at individual and group level remains a vital pathway in public and societal health optimization. Since social hierarchy as social gradient indicates the cause of causes of disease, the implication of Social Determinants of health (SDH) and Epigenomic Determinants of Health (EDH) facilities health disparities marginalization, hence health equity transformation. Given the implication of EDH in disease causation and poorest outcomes in racial/ethnic minorities, there is a commitment in transforming public health to epigenomic public health, nationally and globally.

Aberrant epigenomic modulation, implying the gene and environment interaction in a specific population reflects gene downregulation, impaired protein synthesis and cellular dysfunctionality as abnormal cellular proliferation. For instance, the individual treatment effect heterogeneity and the subpopulation differences in drug response as observed in decreased response of Puerto Rican children with asthma to Albuterol, compared to Mexicans is due to Single Nucleotide Polymorphism (SNP) in the beta-adrenergic receptor as well as socially disadvantaged neighborhood, implying subpopulation variances in epigenomic modulation. While precision medicine (PM) initiative emerges as an attempt to address these treatment heterogeneities. The direction of this initiative in the history of medicine will depend not only on specific risk characterization and targeted therapeutics but on how PM optimizes care through preventive modalities, namely "normo-epigenomic modulation" ("NEM") through everyday equitable resources allocation pertaining to human health.

Epigenomic modulations, which is the gene and environment interaction is explained by the binding of the methyl group (CH3) with the non-coding region or enhancer/promoter region of the gene, termed the C-p-G region, island or shore. This binding termed the DNA methylation process involves the paring of the Cytosine of the CpG with CH3, resulting in CH3-Cytosine, implying mispairing with cytosine rather than guanine, resulting in point mutation. The guanine is one of the 4 nucleobases identified in nucleic acids DNA, while others are classified as cytosine, adenine and thymine. The CpG binding with CH3 that results in CH3-Cytosine , impairs gene expression and cellular dysfunctionality such as abnormal cellular proliferation (malignant neoplasm). Specifically, this epigenomic mechanic process commences with environment such as isolation, depression, structural racism that implicates social signal transduction within the nervous system such as sympathetic pathway, inducing the catecholamine elaboration and the subsequent DNA methylation. Whereas the epigenomic mechanistic process involves histone acetylation, phosphorylation, the most observed mechanistic process remains the DNA methylation, resulting in gene downregulation and impaired expression and the immune system inactivation and dysfunctionality.(Holmes, L Jr,et al., 2020). The aberrant epigenomic mechanistic process may be explained in part by the dysfunctional pathways in the RNA polymerase and well as the DNA methylase involved in the CH3 transition and transfer to the CpG shore of the non-coding or promoter region of the gene. (Holmes, L Jr., et al. 2020).

Racial and ethnic disparities in disease development and health outcomes reflect fundamentally the exposure effect or function of socio-epigenomics, implying gene-social environment interaction that influences rapid response to cellular injury or damage (plasticity), and not sub-population genetic or cytogenetic differentials, given < 0.05% genetic heterogeneity in genomic subpopulations characterization, comparing blacks/AA with their white counterparts in the US. In transforming health equity in the US and globally, based on health disparities narrowing and ultimate elimination, there is a need to understand SDH and EDH, and their applications in this direction. With subpopulations with limited access and utilization of reliable healthcare, there is a need to allocate equitable social and economic resources as disproportionate universalism in subpopulations equitable health outcomes.

Health disparities as subpopulations differentials by race, ethnicity, sex , sexual orientation, education, poverty or socio-economic level, food insecurity, violence environment, healthcare access and utilization in morbidity , treatment, prognosis, survival and mortality are driven by unfair and unjust allocation of social, economic and environmental conditions related to health, implying social injustice. Since DNA sequencing does not reflect human destiny, gene and environment interaction as epigenomic remains human destiny, implying the understanding of epigenomic mechanistic process in gene expression, transcriptomes, protein synthesis and cell synthesis, division and maturation. The individual or community exposure to stress, isolation, air pollutants, toxic waste, discrimination, malnutrition, poor sanitation, etc., signals aberrant epigenomic modulations that alters the biologic system resulting in pathophysiology and disease development, mortality and survival disadvantage. (Holmes, L Jr., et al. 2020).