The transition from a rural to urban environment in Africa alters the expression of genes involved in cholesterol metabolism: Potential implications for susceptibility to infectious diseases
Radhames Lizardo, NMCSD; Simone Langness, UCSD; David Cauvi, UCSD; Katherine Davenport, RCHSD; Julia Grabowski, RCHSD; Antonio De Maio, UCSD; Stephen Bickler, RCHSD
We have recently reported that expression of the Niemann-Pick C1 (NPC1) protein, the receptor of the Ebola virus, is higher in rural compared to urban populations living in Africa. NPC1 is a transmembrane endosome protein responsible for the transport of internalized cholesterol in other intracellular compartments. We have speculated NPC1 expression is down regulated in urban populations from either reduced rates of infection and/or increased ingestion of fat. In this report, we expand this research and examine whether other genes that regulate cholesterol metabolism are altered in the transition from a rural to urban environment in Africa.Hypothesis:
The transition from a rural to an urban environment in Africa alters the expression of genes that control cholesterol hemostasis. Since cholesterol metabolism pathways are known to play a role in innate immunity; variance in their expression could predispose to infectious susceptibilities.Methods:
We queried gene array data from a study by Igadahor et al, 2008 that examined gene expression in peripheral blood leukocytes of genetically similar nomadic, rural, and dense urban Moroccan Amazigh populations (NCBI, GSE8847). Genes involved in cholesterol metabolism where identified by a literature review. The analysis was performed using the NCBI GEO2R tool with results expressed as an adjusted p value. An adjusted p value of <0.05 was considered statistically significant. Results:
Twenty genes that control cholesterol metabolism were examined. Of the genes analyzed, five had higher expression in rural compared urban populations: NPC2, LDLR, SREBPF2, NR1H3 and SCARB1/SCARB2. These genes are involved in both sterol homeostasis and innate immunity. LDLR and SCARB1 have a role in viral infection such as Hepatitis C and the NPC family in Ebola virus infection. SREBPF2 and NRIH3 are important mediators of the inflammatory response to bacterial infections.Conclusions:
Our data illustrates the important role environmental factors have in altering the expression of genes that control cholesterol metabolism which are now well known to have a critical role in the immune response to a variety of pathogens. Further, our findings could provide important insight into factors that determine susceptibility to both communicable and non-communicable diseases in a variety of populations.