Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana.
Department of Clinical Microbiology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Hum Genomics. 2017 Nov 9;11(1):26. 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.
淋巴水肿（LE）是丝虫感染的一种慢性临床表现，其特征为淋巴功能障碍以及随后间质空间中富含蛋白质的液体积聚 - 淋巴丝虫病。许多研究已经确定了与原发性和继发性 LE 相关的单核苷酸多态性（SNPs）。为了评估与淋巴丝虫病引起的 LE 相关的 SNPs，设计了一项加纳无关志愿者的横断面研究，以将 285 名 LE 患者作为病例进行基因分型，将 682 名感染但无病理学的患者作为对照。对 64 个基因中的 131 个 SNPs 进行了基因分型。这些基因是根据它们在炎症过程、血管生成/淋巴管生成以及肿瘤发生过程中的细胞分化中的作用选择的。
在三个基因中的五个 SNP 中发现了具有名义意义的遗传关联：血管内皮生长因子受体-3（VEGFR-3）rs75614493、基质金属蛋白酶-2（MMP-2）rs1030868 和 rs2241145 中的两个 SNP 以及癌胚抗原相关细胞粘附分子-1（CEACAM-1）rs8110904 和 rs8111171 中的两个 SNP。通路分析显示了血管生成/淋巴管生成途径中基因的相互作用。与对照组相比，LE 病例的 MMP-2 和 CEACAM-1 血浆水平均显著升高。与相关 SNP 的功能特征鉴定出 CEACAM-1 的基因型 GG 是影响血浆浓度表达的变体，这是本研究中观察到的新发现。
在 MMP-2、CEACAM-1 和 VEGFR-3 基因中发现的 SNP 关联表明，血管生成/淋巴管生成途径在 LE 临床发展中很重要。
