Wednesday, July 16, 2008


From Times OnlineJuly 16, 2008

Scientists make gene link to African HIV epidemicMark Henderson, Science Editor
A genetic variant peculiar to Africans substantially raises their risk of infection with HIV, according to research that suggests evolved susceptibility may be helping to drive the continent’s Aids epidemic.

The 90 per cent of Africans who carry the DNA variation are 40 per cent more likely to contract HIV than are those without it, following similar exposure to the virus, scientists from Britain and the United States have found.

As the genetic change is very common among people of African ancestry, but virtually unknown among other ethnic groups, it could partially explain why HIV-Aids is so much more prevalent in sub-Saharan Africa than elsewhere in the world.

The United Nations estimates that 22.5 million people in the region are HIV positive, accounting for more than two thirds of the global total of approximately 33.2 million people.

The genetic variant, known as “Duffy-negative”, is so common in Africa that it could be responsible for about 11 per cent of the continent’s HIV burden, or 2.5 million cases, scientists said.

“It is an Africa-specific variant, which is why it’s so interesting in the context of Aids research,” said Robin Weiss, Professor of Infection and Immunity at University College London, a member of the study team.

“It could certainly be a contributing factor to the scale of the epidemic in sub-Saharan Africa. It’s the first time, so far as we understand, that a genetic factor that increases susceptibility to infection has come into play.”

Patterns of sexual behaviour are also involved in the African epidemic, which predominantly affects heterosexuals. In other parts of the world, HIV-Aids mainly affects homosexuals, sex workers and intravenous drug users.

The Duffy-negative gene has probably spread so widely through the African population because it is known to confer resistance to a form of malaria called Plasmodium vivax. Professor Weiss believes that it may also once have increased resistance against a precursor of the most deadly malaria parasite, Plasmodium falciparum.

These traits would have been highly advantageous in Africa in the evolutionary past. As HIV is a new human pathogen, which is thought to have jumped from chimpanzees to people between 1910 and 1950, the gene’s effect on the virus would have had no negative consequences until recently.

“The big message here is that something that protected against malaria in the past is now leaving the host more susceptible to HIV,” Professor Weiss said.

Matthew Dolan, of the San Antonio Military Medical Centre in Texas, another author of the research, said: “After thousands of years of adaptation, this Duffy variant rose to high frequency because it helped protect against malaria.

“Now, with another global pandemic on the scene, this same variant renders people more susceptible to HIV. It shows the complex interplay between historically important diseases and susceptibility in contemporary times.”

The Duffy variant, however, is not without benefits for HIV. The study, which is published in the journal Cell Host & Microbe, found that on average Duffy-negative people who do become infected live for about two years longer than those without the variant.

Professor Sunil Ahuja, of the University of Texas Health Science Center at San Antonio, who led the research, said: “It turns out that having this variation is a double-edged sword. The finding is another valuable piece in the puzzle of HIV-Aids genetics.

“It’s well known that individuals vary in their susceptibility to HIV and that after infection occurs, the disease progresses at variable rates. The mystery of variable infection and progression was originally thought to be mainly the result of viral characteristics, but in recent years it has become evident that there is a strong host genetic component.”

In the study, the scientists examined a large cohort of US Air Force personnel, including more than 1,200 who are HIV positive, who have been followed for nearly 22 years. This group was deemed particularly appropriate for investigation, as they have similar social backgrounds and patterns of sexual behaviour and drug use, which can all affect HIV susceptibility.

The Duffy-negative genotype was found almost exclusively among African-Americans. Those African-Americans with the variant were 40 per cent more likely to be HIV positive than those who lacked it.

The mechanisms by which the Duffy-negative variant increases the risk of infection, yet prolongs the illness, remain unknown, Professor Weiss said.

The gene encodes a protein found mainly on the surface of red blood cells. It is possible that the less risky variant turns these into “sponges” that soak up the virus, so that it becomes less likely to infect the T-cells of the immune system, which are killed off by the disease.

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