Gene Mutation May Reduce Risk of HIV

THURSDAY, Aug. 23 (HealthScoutNews) -- People who inherit just one copy of a mutated gene are at a substantially lower risk of being infected with the AIDS virus, new research shows.

Scientists have known for years that two copies of this gene -- one from each parent -- act like a vaccination against HIV . But the new study shows that having only one copy can reduce the risk of contracting the virus by 70 percent.

"There has been some conflicting data on whether [people with only one copy of the gene mutation had] any resistance to HIV," says lead investigator Michael Marmor, a professor of medicine and environmental medicine at New York University School of Medicine. "The consensus was that there was no protection, though there were some hints that [the mutation] might confer protection. What we wanted to do was prove it or not prove it."

HIV usually disables the body's immune system by fusing with what's called CCR5 receptors, which lie on the surface of immune cells called T-helper cells. There are thousands of CCR5 receptors on T-helper cells.

People who have a copy of the genetic mutation known as the delta-32 mutation -- one from each parent -- have no working copies of the CCR5 receptors and are therefore resistant to HIV even with repeated exposure.

"About 1 percent of Caucasians carry both copies of the mutation," Marmor says. "The mutation is very rare in non-Caucasians."

Marmor and colleagues from New York, Boston, Seattle and San Francisco looked for either one copy or two copies of the delta-32 mutation among a large cohort of HIV-negative people who were at risk for the disease.

"We included in the cohort those who were sexually at risk -- both men and women -- and those at risk of using illicit drugs by injection," Marmor says.

The researchers followed almost 3,000 participants at the four centers for 18 months, testing them for HIV every six months and interviewing them about their sexual behavior. Female participants ended up not being included in the final results because there were too few to be statistically significant, Marmor says.

"We found that among Caucasian gay men, there were 32 who were homozygous [two copies of the mutation], 279 who were heterozygous [one copy] and 1,220 with no copies of the mutation," Marmor says. "And what we found was that incidence in the heterozygous group of the risk of infection was cut by 70 percent compared to those who had no copies of the mutation.

He adds, "It was quite a surprising finding, and it brings together the data that progression of HIV is slowed in those who are heterozygous, and their risk of infection is reduced."

The findings are published in the August issue of the Journal of Acquired Immune Deficiency Syndrome.

The findings are significant but have no immediate application, says Greg Gonsalves, director of treatment advocacy for the Gay Men's Health Crisis in New York City. Nevertheless "it's clearly an advance in our understanding of susceptibility to HIV infection and how HIV infects cells. And each small step is an advance in our battle against the disease."

Gonsalves says no one is sure why the delta-32 mutation is found only in white people. "There's some sense that the mutation of the gene appeared for some other reason, in response to something within the population's development. Lots of genes track with people of different descent and different geographical location. This one just seems to have settled in people of Northern European heritage."

"The finding could provide a means for reducing susceptibility for HIV," Marmor continues. "It certainly is appealing in providing new understanding of how we might slow down the spread of the virus. Is it reducing the number of CCR5 receptors? I think we need more research on that."