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Gene variant increases Africans' HIV risk

21 July 2008

By Evelyn Harvey

Appeared in BioNews 467

A form of a gene that protects many Africans from certain forms of malaria increases HIV (human immunodeficiency virus) infection risk, according to a new study published in the journal Cell Host and Microbe. Researchers Professor Sunil K Ahuja, from The University of Texas Health Science Center at San Antonio, and Professor Robin Weiss, from University College London's department of Infection and Immunity, drew their conclusions from genetic data collected during a 25-year study of 3,400 Americans of different ethnic backgrounds.

The gene involved encodes a receptor protein, called DARC (Duffy antigen receptor for chemokines) that is expressed on blood cell surface. Chemokines are chemical messengers used by the immune system to coordinate inflammation. Malaria can use DARC to infect red blood cells. The variant gene common in Africans carries a mutation leading to a loss of DARC expression, preventing malaria from gaining a foothold. However, DARC also influences HIV infection. 'The big message here is that something that protected against malaria in the past is now leaving the host more susceptible to HIV', said Professor Weiss. He continued: 'In sub-Saharan Africa, the vast majority of people do not express DARC on their red blood cells and previous research has shown that this variation seems to have evolved to protect against a particular form of malaria. However, this protective effect actually leaves those with the variation more susceptible to HIV'.

The research shows a 40 per cent increase in the risk of HIV infection in African-Americans with the DARC mutation, compared to those with normally expressed DARC. The study goes some way to explaining the devastating impact of HIV on sub-Saharan Africa. Genetic susceptibility, not social factors alone, may account for the high rates of infection. This is the first uniquely African genetic link to HIV to be identified. A mutation in another chemokine receptor, called CCR5, was previously found to confer increased resistance to HIV in around one per cent of Caucasians.

Surprisingly, the researcher found that individuals with the DARC variant who become infected with HIV live slightly longer than HIV-infected individuals with non-mutant DARC. The reasons for that remain unclear, says Weiss. The findings could have implications for the understanding and treatment of HIV and AIDS. However, further work on different populations needs to be done to confirm the findings.

'This is a provocative paper that will stimulate research in the field', says Cheryl Winkler, who studies the genetics of infectious diseases at the US National Cancer Institute in Maryland, adding: 'but I don't believe this is a done deal'.

Nature News | 16 July 2008
The Guardian | 17 July 2008
ScienceDaily | 17 July 2008
BBC News Online | 16 July 2008


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