Malaria is one of the most prevalent communicable diseases, resulting in over 500 million clinical cases and at least 1 million deaths per year. The greatest burden of mortality due to malaria is found in sub-Saharan Africa. Malaria is known to be a major selective force in the evolution of humans; however, the extent of malaria's selection on the human genome is unknown. Plasmodium, the protozoan responsible for malaria, must scavenge lipids and associated apolipoproteins from host blood in order to develop and replicate in hepatocytes and erythrocytes. This requirement may have influenced selection of protective host apolipoprotein genotypes. Apolipoproteins are heavily involved in cardiovascular function. Interestingly, certain apolipoprotein polymorphisms have previously been implicated in the increased risk of cardiovascular disease in African-Americans. The proposed work seeks to examine the hypothesis that apolipoprotein polymorphisms are selected for by malaria and that polymorphism expression influences malariometric indices in those infected. Therefore, we aim to: 1) Determine the frequency of certain human genetic apolipoprotein polymorphisms in a population in Gabon, West Africa where malaria transmission is seasonal and two populations in PNG where malaria has been historically absent or present using polymerase chain reaction and direct sequencing 2) Establish associations between apolipoprotein polymorphisms and malaria by comparing polymorphism frequencies among aforementioned populations and those recorded in the NCBI databases and literature 3) Identify associations between apolipoprotein and erythrocyte genotypes and malariometric indices in our three distinctive populations using statistical analysis. Relevance: Investigation of apolipoprotein genotype frequencies in populations affected by malaria may provide insight into the evolutionary impact of malaria on the human genome. Increased knowledge regarding protective traits can be used in the field of pharmacogenomics to produce vaccines and treatments that will be of maximum benefit to the greatest amount of people. These findings may also explain differences in apolipoprotein genotype frequencies and the genetics of cardiovascular disease in African-Americans. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31GM086134-01
Application #
7547357
Study Section
Special Emphasis Panel (ZRG1-HOP-Z (29))
Program Officer
Toliver, Adolphus
Project Start
2008-08-29
Project End
2011-08-28
Budget Start
2008-08-29
Budget End
2009-08-28
Support Year
1
Fiscal Year
2008
Total Cost
$29,971
Indirect Cost
Name
New York University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Rougeron, Virginie; Woods, Caira M; Tiedje, Kathryn E et al. (2013) Epistatic Interactions between apolipoprotein E and hemoglobin S Genes in regulation of malaria parasitemia. PLoS One 8:e76924