Genetics of Lymphedema and Hydrocele in Filariasis

• Antragsteller: Dr. Kenneth Pfarr, Ph.D.
• Mitantragsteller: Professor Dr. Ohene Adjei
• Fachliche Zuordnung: Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
• Förderung: Förderung von 2009 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 68646942

Filarial nematodes infect ~120 million people in the tropics. The disease is a neglected disease and, until recently, filarial infections were thought to only cause morbidity, not death. The majority of infected individuals have no or transient pathology (e.g. recurrent debilitating fever), while others suffer more severe pathologies including lymphedema of the limbs (LE, estimated worldwide prevalence of 7%) or hydrocele (fluid build-up in the tunica vaginalis of the scrotum, estimated prevalence of 30-50% of infected men). Pathology and parasite load are inversely correlated, suggesting that containment of parasites by the immune system leads to inflammation-related disease. Studies have shown that susceptibility to infection, parasite load and lymphatic pathology cluster in families independent of household and environment. However, only a few studies have looked for genes associated with lymphatic filariasis. We recently found a highly significant association of single nucleotide polymorphisms (SNPs) of Vascular Endothelial Growth Factor-A (VEGF-A) promoter with hydrocele in Ghanaian patients. Understanding the genetics of lymphatic filariasis could aid in ameliorating pathology other than invasive, expensive surgery. Knowing genetic markers for LE or hydrocele could also provide a way to identify persons at risk before pathology is seen and might become the basis for development of a rapid screening test. To identify such genetic markers, we will genotype 400 LE, 400 hydrocele and 400 infected patients without pathology for SNPs of pro- and anti-inflammatory cytokines and cytokine receptors, VEGFs and VEGF receptors for association with the different disease manifestations in lymphatic filariasis. Using a subset of the patients, SNPs found to have an association with pathology will be analyzed for function (e.g. ELISA to measure cytokine levels for a SNP that alters cytokine production). This proposal will strengthen the existing collaboration between the universities of Bonn, Germany and Kumasi, Ghana, and will train and further sustain a new generation of primary investigators to continue this collaboration.

• DFG-Verfahren: Sachbeihilfen
• Internationaler Bezug: Ghana
• Beteiligte Person: Professor Dr. Achim Hoerauf