Human Genetic Polymorphisms in Malaria-endemic Areas
Principal Investigator: CAIRA WOODS
Abstract: DESCRIPTION (provided by applicant): 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.
Funding Period: 2008-08-29 - 2011-08-28
more information: NIH RePORT
- Epistatic Interactions between apolipoprotein E and hemoglobin S Genes in regulation of malaria parasitemiaVirginie Rougeron
Department of Microbiology, Division of Medical Parasitology, New York University School of Medicine, New York, New York, United States of America
PLoS ONE 8:e76924. 2013..These findings have significance for understanding host determinants of regulation of malaria parasite density, the design of clinical trials as well as studies of co-infection with Plasmodium and other pathogens. ..