The Rural-Urban Divide: Insights from Immuno-Genetic Profiles and Implications for Health

Abstract

Population disparities in health and disease have been observed and amply documented. While often attributable to genetic underpinnings, such disparities extend beyond population genetic predisposition to include environmental and geographic determinants, most pronouncedly the division between rural and urban lifestyles. Under such influences, genes and gene products may become affected by epigenetic factors, microbial modifiers including infections, and the body microbiome that ultimately shapes the outcome of a complex milieu of protein networks. Retrospective, demographic, genotype, and expression data from two rural populations in eastern Sudan were analysed for genotype, allele frequency distribution, Hardy-Weinberg equilibrium, and expression profiles using an array panel of Th1, Th2, and Th3 genes in a subset of the rural population sample against matched urban controls. Differences between urban and rural samples were observed in the departure from HWE, with an excess of heterozygosity in the rural sample. In the Th1, Th2, and Th3 array, cytokines were consistently overexpressed in the rural cohort compared to the urban cohort and were replicated in 7 selected genes that are associated with chronic diseases amongst urban dwellers in contrast to rural village inhabitants. IgE levels, as a feature of parasitic infections, are another difference to include in that dichotomy. Gene expression appears to be more exposed to the overall outcome of genetic variations, including the interaction with environmental influences within and outside the body. Here, it may be gathered from the contrast in the expression patterns between the rural and urban samples. The presence of signals of natural selection in genes that are key to certain biological functions, such as CD40L and FasL, and the sharp contrast between urban and rural populations in gene variants distribution and expression patterns, may provide important clues towards understanding the disparity between human communities in non-communicable diseases of lifestyle as well as some of the emerging infectious diseases.