Urbanization Alters the Expression of NADPH Oxidase and Superoxide Dismutase Genes
Author(s):
Stephen Bickler; Victor DeCos; Sneha Nicholson; Sean Flynn; Hari Thangarajah; David Lazar; Karen Kling; Timothy Fairbanks; Antonio De Maio
Background:
Urbanization in low-income countries represents an important inflection point in the epidemiology of communicable and non-communicable diseases. Populations living in undeveloped rural areas experience a high burden of chronic and recurrent infections, whereas those living in cities take on a pattern of non-communicable diseases (NCDs). The molecular mechanisms that underlie this epidemiological transition remain poorly understood. NADPH oxidases (NOX) have an important role in fighting infection via production of the superoxide radical, and in the pathophysiology of NCDs such as atherosclerosis and hypertension. This research begins to explore whether urbanization alters NOX function and antioxidant pathways.
Hypothesis:
Urbanization alters the expression of selected NOX genes (CYBA, CYBB) and genes encoding superoxide dismutase (SOD1, SOD2). CYBA and CYBB encode the cytochrome b alpha and beta chains that comprise cytochrome b (-245), a critical component of the microbicidal oxidase system of innate immune cells. SOD1 and 2 are important antioxidants that destroy free superoxide radicals.
Methods:
We compared the expression of the NOX and SOD genes in a rural and urban population living in Morocco. The Moroccan dataset (NCBI GSE8847) contains information on the expression of peripheral blood leukocyte genes from genetically similar nomadic, rural, and high-density urban Amazigh populations (PLos Genet 2008, 4(4): e1000052). Adjusted p values were extracted from Dataset S2 provided in the Supporting Information Section of the Idaghdour et al. 2008 manuscript, and corresponded specifically to the rural-urban comparison. A p value <0.05 was considered significant.
Results:
Moroccans living in rural areas had significantly higher expression of the CYBB gene, compared to those living in urban areas (p=2.66e-8). Expression of the CYBA gene approached significance (p= .08). The expression of the antioxidant gene SOD2 was increased in the urban population, compared to the rural population (p = .0018). Urbanization had no effect on the expression of the SOD1 gene.
Conclusions:
These preliminary results suggest urbanization alters the expression of genes that control NADPH oxidase and superoxide dismutase. We hypothesize that the greater expression of NOX genes in the rural population might relate to higher rates of infection, while the increased expression of the SOD2 gene in the urban population may represent an adaptive response to greater oxidative stress. The increased prevalence of NCDs in urban populations might, in part, relate to an imbalance of oxidant species and antioxidant defenses. Further research is needed to investigate how chronic and recurrent infection affect the activity of NADPH oxidases and associated antioxidant pathways.