Genetics of Lymphedema and Hydrocele in Lymphatic Filariasis

• Applicant: Dr. Kenneth Pfarr, Ph.D.
• Co-Applicants: Professor Dr. Ohene Adjei; Professor Dr. Alex Yaw Debrah, Ph.D.; Dr. Williams Makunde, Ph.D.
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 215074314

Filarial nematodes infect >120 million people in developing countries, yet only ~7% develop lymphedema and ~50% of men develop hydrocele, causing severe morbidity. To elucidate the genetic basis for filarial pathology, we designed a cross-sectional study of unrelated Ghanaian volunteers to genotype single nucleotide polymorphisms (SNPs) in 400 lymphedema, 400 hydrocele and 400 infected without pathology. Currently 119 out of the 148 chosen SNPs have been genotyped and are being analyzed. Six SNPs in 6 genes were associated with lymphedema; 5 SNPs in 4 genes were associated with hydrocele; 7 SNPs in 7 genes were associated with presence of larvae in the blood. Two SNPs in the caveolin-1 gene (regulates TGF-β signaling; interacts with the endothelin B receptor) formed a haplotype associated with hydrocele. A SNP in matrix metalloprotease-2 (involved in tissue remodeling) was associated with both lymphedema and hydrocele. To use the associated SNPs as biomarkers for indentifying persons at greater risk of developing pathology, we propose to: 1) functionally characterize the SNPs already identified, 2) elucidate further SNPs and phenotypes in genes of the angiogenesis pathway, and 3) recruit a replicate group in Tanzania to confirm that the SNPs are associated with filarial pathology.

• DFG Programme: Research Grants
• International Connection: Ghana, Tanzania
• Participating Person: Professor Dr. Achim Hoerauf