Editors' ChoiceSchistosomiasis

Fishermen and Farmers Share SNPs and Severe Fibrosis

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Science Translational Medicine  21 Oct 2009:
Vol. 1, Issue 3, pp. 3ec10
DOI: 10.1126/scitranslmed.3000507

So much for the protective power of skin. The schistosome worm scoffs at this largest organ in the human body. When schistosome larvae are released from their intermediate hosts, freshwater snails, these parasites burrow through the unbroken skin of their ultimate hosts—humans who wade in tropical waters. Some schistosomes take up residence and lay eggs in the space around the hepatic portal vein, spurring liver inflammation that can persist for years. Five to ten percent of schistosome-infected individuals develop severe fibrosis of the liver, which often is fatal, but there is no way to identify these susceptible patients among the 350 million who are infected worldwide. Now, Dessein et al. report on their study of populations at risk for schistosomiasis—Chinese, Sudanese, and Brazilian subjects who live near worm-infested waters—which identified single-nucleotide polymorphisms (SNPs) around the connective tissue growth factor (CTGF) gene that correlate with liver fibrosis in schistosomiasis patients. CTGF is overexpressed in fibrotic livers and encodes a profibrogenic growth factor produced by liver cells. The fact that these SNPs were found in ethnically and geographically diverse populations strengthens their significance, especially when one considers that these populations contract the disease from two distinct schistosome species. CTGF made from genes carrying the SNPs displayed altered binding to nuclear proteins, suggesting that the mutated polypeptides might alter the expression of genes that contribute to liver fibrosis. These findings do not rule out the existence of other biological pathways that give rise to this phenotype. However, these SNPs do point the way toward possible new drug and diagnostic targets for schistosomiasis-associated liver fibrosis.

A. Dessein et al., Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with schistosomes. J. Exp. Med. 12 October 2009 (10.1084/jem.20090383). [Abstract]

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