The Genetics of Human Schistosomiasis Infection Intensity and Liver Disease: A Review.

Schistosomiasis remains the fourth most prevalent parasitic disease affecting over 200 million people worldwide. Control efforts have focussed on the disruption of the life cycle targeting the parasite, vector and human host. Parasite burdens are highly skewed, and the majority of eggs are shed into the environment by a minority of the infected population. Most morbidity results from hepatic fibrosis leading to portal hypertension and is not well-correlated with worm burden. Genetics as well as environmental factors may play a role in these skewed distributions and understanding the genetic risk factors for intensity of infection and morbidity may help improve control measures. In this review, we focus on how genetic factors may influence parasite load, hepatic fibrosis and portal hypertension. We found 28 studies on the genetics of human infection and 20 studies on the genetics of pathology in humans. and infection intensity have been showed to be controlled by a major quantitative trait locus , on chromosome 5q31-q33 containing several genes involved in the T2 immune response, and three other loci of smaller effect on chromosomes 1, 6, and 7. The most common pathology associated with schistosomiasis is hepatic and portal vein fibroses and the quantitative trait locus on chromosome six has been linked to intensity of fibrosis. Although there has been an emphasis on T2 cytokines in candidate gene studies, we found that four of the five QTL regions contain T17 pathway genes that have been included in schistosomiasis studies: and in and in 6p21-q2, in 1p21-q23 and in . The T17 pathway is known to be involved in response to schistosome infection and hepatic fibrosis but variants in this pathway have not been tested for any effect on the regulation of these phenotypes. These should be priorities for future studies.