Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
Front Cell Infect Microbiol. 2022 Apr 12;12:871545. doi: 10.3389/fcimb.2022.871545. eCollection 2022.
infections, which lead to local inflammatory responses to schistosome eggs trapped in host tissues, can result in long-term, severe complications. The development of schistosomiasis may result from a complex interaction between the pathogenic, environmental, and host genetic components. Notably, the genetic factors that influence the development of schistosomiasis complications are poorly understood. Here we performed a genome-wide association study on multiple schistosomiasis-related phenotypes of 637 unrelated schistosomiasis patients in the Chinese population. Among three indicators of liver damage, we identified two novel, genome-wide significant single-nucleotide polymorphisms (SNPs) rs34486793 ( = 1.415 × 10) and rs2008259 ( = 6.78 × 10) at locus 14q32.2 as well as a gene, , at 20q13.31 (index rs62205791, = 6.52 × 10). These were significantly associated with serum levels of hyaluronic acid (HA). In addition, and at 19q13.33 (index rs62132778, = 1.72 × 10) were significantly associated with serum levels of aspartate aminotransferase (AST), and at 15q22.2 (index rs12442303, = 4.39 × 10) was significantly associated with serum levels of albumin. In schistosomiasis clinical signs, at 3p21.1 (index rs2239548) was associated with portal vein diameter (PVD) class, an indicator of portal hypertension, and at 10q11.23 (index rs1258172) was related to ascites grade. We also detected an increased expression of these six genes in livers of mice with severe schistosomiasis. Summary data-based Mendelian randomization analyses indicated that , and were pleiotropically associated with PVD class, HA and AST, respectively.
感染会导致在宿主组织中被困的血吸虫卵引起局部炎症反应，从而导致长期的严重并发症。血吸虫病的发展可能是由病原、环境和宿主遗传因素的复杂相互作用引起的。值得注意的是，影响血吸虫病并发症发展的遗传因素还了解甚少。在这里，我们对中国人群中 637 名无血缘关系的血吸虫病患者的多种与血吸虫病相关的表型进行了全基因组关联研究。在三个肝损伤指标中，我们在 14q32.2 位置鉴定出两个新的全基因组显著的单核苷酸多态性（SNP）rs34486793（ = 1.415×10）和 rs2008259（ = 6.78×10），以及 20q13.31 位置的一个基因（ = 6.52×10）。这些 SNP 与透明质酸（HA）的血清水平显著相关。此外，19q13.33 位置的（ = 1.72×10）和 15q22.2 位置的（ = 4.39×10）与天门冬氨酸氨基转移酶（AST）的血清水平显著相关，而 15q22.2 位置的（ = 4.39×10）与白蛋白的血清水平显著相关。在血吸虫病的临床症状中，3p21.1 位置的（ = 1.72×10）与门静脉直径（PVD）分类相关，这是门脉高压的一个指标，而 10q11.23 位置的（ = 4.39×10）与腹水分级相关。我们还检测到在严重血吸虫病小鼠的肝脏中这六个基因的表达增加。基于汇总数据的孟德尔随机化分析表明，、和分别与 PVD 分类、HA 和 AST 呈多效性相关。
