Genetic variants that increase infectious diseases risk identified

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Washington, May 20 (ANI): Scientists have identified new genetic variants that increase susceptibility to several infectious diseases including tuberculosis and malaria.

With greater understanding of the role of the gene implicated, researchers from the Wellcome Trust Centre for Human Genetics at the University of Oxford, Singapore's Agency for Science, Technology and Research (A*STAR) and National University Health System (NUHS) hope that the findings could one day lead to better therapies and vaccines.

Environmental factors such as malnutrition and poor hygiene can account for a large proportion of an individual person's susceptibility to infectious diseases, but it's clear that this is not the whole story. Studies of twins and adopted persons indicate that genetics also plays a role.

The team analysed genes from over 8,000 people at clinical sites in Malawi, Kenya, Vietnam, Hong Kong and The Gambia, over a period of 5 years. In particular, they were looking for genetic variants that might contribute to susceptibility to tuberculosis, malaria and serious bacterial infections of the blood, or bacteraemia.

Their findings reveal a striking association with a gene called CISH and increased risk of susceptibility to these infectious diseases.

CISH encodes a protein that is involved in the immune response to infectious diseases. It plays a role in dampening down messaging signals between cells of the immune system.

A panel of five different genetic variants was identified within the CISH gene. Within the population studied, having just one of these variants increased susceptibility to disease by 18 percent compared with somebody who does not have any 'risk' variants.

One variant in particular accounted for most of the genetic association with disease. Functional studies carried out in Singapore showed that blood cells from healthy Chinese volunteers carrying that variant had lower levels of the CISH protein overall than individuals with the normal variant.

This suggests that CISH exerts a significant genetic influence on our immune response.

Dr Chiea C. Khor from A*STAR's Singapore Institute for Clinical Sciences (SICS), who co-led the studies in Singapore, commented: "It's not clear from our study why having a reduced level of CISH associates with increased susceptibility to multiple infectious diseases, but it does suggest that CISH is a key regulator of the immune system. We hope that our findings will encourage clinical research to better understand the immunological processes that are going on, with a view to identifying targets for therapeutic intervention and the development of better therapies and accines." (ANI)

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