Background

Non-communicable diseases (NCDs), such as atherosclerosis and cancers, are a leading cause of death worldwide. An important, yet poorly explained epidemiological feature of NCDs is their low incidence in under developed areas of low-income countries and rising rates in urban areas.

Methods

With the goal of better understanding how urbanization increases the incidence of NCDs, we provide an overview of the urbanization process in sub-Saharan Africa, discuss gene expression differences between rural and urban populations, and review the current NCD determinant model. We conclude by identifying research priorities.

Results

Declining rates of chronic and recurrent infection are the hallmark of urbanization in sub-Saharan Africa. Gene profiling studies show urbanization results in complex molecular changes, with almost one-third of the peripheral blood leukocyte transcriptome altered. The current NCD determinant model could be improved by including a possible effect from declining rates of infection and expanding the spectrum of diseases that increase with urbanization.

Conclusions

Urbanization in sub-Saharan Africa provides a unique opportunity to investigate the mechanism by which the environment influences disease epidemiology. Research priorities include: (1) studies to define the relationship between infection and risk factors for NCDs, (2) explaining the observed differences in the inflammatory response between rural and urban populations, and (3) identification of animal models that simulate the biological changes that occurs with urbanization. A better understanding of the biological changes that occur with urbanization could lead to new prevention and treatment strategies for some of the most common surgical diseases in high-income countries.

Urbanization in low-income countries represents an important inflection point in the epidemiology of disease, with rural populations experiencing high rates of chronic and recurrent infections and urban populations displaying a profile of noncommunicable diseases. To investigate if urbanization alters the expression of genes encoding mitochondrial proteins, we queried gene microarray data from rural and urban populations living in Morocco (GSE17065). The R Bioconductor packages edgeR and limma were used to identify genes with different expression. The experimental design was modeled upon location and sex. Nuclear genes encoding mitochondrial proteins were identified from the MitoCarta2.0 database. Of the 1158 genes listed in the MitoCarta2.0 database, 847 genes (73%) were available for analysis in the Moroccan dataset. The urban-rural comparison with the greatest environmental differences showed that 76.5% of the MitoCarta2.0 genes were differentially expressed, with 97% of the genes having an increased expression in the urban area. Enrichment analysis revealed 367 significantly enriched pathways (adjusted p value < 0.05), with oxidative phosphorylation, insulin secretion and glucose regulations (adj.p values = 6.93E-16) being the top three. Four significantly perturbed KEGG disease pathways were associated with urbanization-three degenerative neurological diseases (Huntington's, Alzheimer's, and Parkinson's diseases) and herpes simplex infection (false discover rate corrected p value (PGFdr) < 0.2). Mitochondrial RNA metabolic processing and translational elongation were the biological processes that had the greatest enrichment (enrichment ratios 14.0 and 14.8, respectively, FDR < 0.5). Our study links urbanization in Morocco with changes in the expression of the nuclear genes encoding mitochondrial proteins.