Single nucleotide polymorphisms in the angiogenic and lymphangiogenic pathways are associated with lymphedema caused by Wuchereria bancrofti

• Published in: Human genomics Vol. 11; no. 1; p. 26
• Main Authors: Debrah, Linda Batsa, Albers, Anna, Debrah, Alexander Yaw, Brockschmidt, Felix F, Becker, Tim, Herold, Christine, Hofmann, Andrea, Osei-Mensah, Jubin, Mubarik, Yusif, Fröhlich, Holger, Hoerauf, Achim, Pfarr, Kenneth
• Format: Journal Article
• Language: English
• Published: England BioMed Central 09.11.2017; BMC
• Subjects: Angiogenesis; Genotypes; Lymphangiogenesis; Lymphatic filariasis; Primary Research; Single nucleotide polymorphisms; Angiogenesis; Single nucleotide polymorphisms; Lymphangiogenesis; Lymphatic filariasis; Genotypes
• ISSN: 1479-7364; 1473-9542; 1479-7364
• DOI: 10.1186/s40246-017-0121-7

Lymphedema (LE) is a chronic clinical manifestation of filarial nematode infections characterized by lymphatic dysfunction and subsequent accumulation of protein-rich fluid in the interstitial space-lymphatic filariasis. A number of studies have identified single nucleotide polymorphisms (SNPs) associated with primary and secondary LE. To assess SNPs associated with LE caused by lymphatic filariasis, a cross-sectional study of unrelated Ghanaian volunteers was designed to genotype SNPs in 285 LE patients as cases and 682 infected patients without pathology as controls. One hundred thirty-one SNPs in 64 genes were genotyped. The genes were selected based on their roles in inflammatory processes, angiogenesis/lymphangiogenesis, and cell differentiation during tumorigenesis. Genetic associations with nominal significance were identified for five SNPs in three genes: vascular endothelial growth factor receptor-3 (VEGFR-3) rs75614493, two SNPs in matrix metalloprotease-2 (MMP-2) rs1030868 and rs2241145, and two SNPs in carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1) rs8110904 and rs8111171. Pathway analysis revealed an interplay of genes in the angiogenic/lymphangiogenic pathways. Plasma levels of both MMP-2 and CEACAM-1 were significantly higher in LE cases compared to controls. Functional characterization of the associated SNPs identified genotype GG of CEACAM-1 as the variant influencing the expression of plasma concentration, a novel finding observed in this study. The SNP associations found in the MMP-2, CEACAM-1, and VEGFR-3 genes indicate that angiogenic/lymphangiogenic pathways are important in LE clinical development.