Depending on the study population, each additional CCL3L1 copy lowered the risk of acquiring HIV by between 4.5 and 10.5 percent. Additionally, below-average CCL3L1 copy numbers were associated with a 39 to 260 percent higher risk of rapid progression to AIDS.

People with more copies of the gene are less likely to become infected with the virus or to develop AIDS than those of the same geographical ancestry -- say European Americans, for example -- who have fewer copies of the gene, researchers found.

New Medical Approaches to Fighting AIDS Possible

Scientists believe that this discovery could lead to a screening test that identifies people who have a higher or lower susceptibility to HIV/AIDS, potentially enabling clinicians to adapt treatment regimens, vaccine trials and other studies accordingly. The research appears January 6 in Science Express, an online publication of the journal Science.

"Individual risk of acquiring HIV and experiencing rapid disease progression is not uniform within populations," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). "This important study identifies genetic factors of particular groups that either mitigate or enhance one's susceptibility to infection and disease onset.

"In a broader sense," says Dr. Fauci, "it also suggests how the immune systems of individuals with different geographical ancestries might have evolved in response to microbial stresses and how these differences in the immune system might result in medical approaches to thwart HIV/AIDS or other infections that vary among groups."

Average Number of Gene Copies Varies by Group

The senior authors of the study are Sunil K. Ahuja, M.D., of the University of Texas Health Science Center and the Veterans Administration Center for AIDS and HIV-1 Infection in San Antonio, and Matthew J. Dolan, M.D., of the U.S. Air Force's Wilford Hall Medical Center and Brooks City-Base in San Antonio.

They analyzed blood samples from more than 4,300 HIV-positive and HIV-negative people of different ancestral origins to determine the average number of CCL3L1 gene copies in each group.

They found that, for example, HIV-negative African-American adults had an average of four CCL3L1 copies, while HIV-negative European-American and Hispanic-American adults averaged two and three copies, respectively.

Individuals More or Less Susceptible Based on Deviation from Average

This does not mean that European Americans are more prone to HIV/AIDS than other populations. Rather, using the average CCL3L1 gene copy number as a reference point for each group, the authors found that individuals with fewer CCL3L1 copies than their population's average were more susceptible to HIV infection and rapid progression to AIDS. People with greater-than-average CCL3L1 gene copies, in contrast, were less prone to infection by HIV or to rapid progression to AIDS.

Depending on the study population, each additional CCL3L1 copy lowered the risk of acquiring HIV by between 4.5 and 10.5 percent. Additionally, below-average CCL3L1 copy numbers were associated with a 39 to 260 percent higher risk of rapid progression to AIDS.

To further test the impact of CCL3L1 copies on HIV/AIDS risk, the researchers then studied variations in the CCR5 gene that they had previously linked to varying rates of AIDS progression. They found that individuals who possessed a low CCL3L1 copy number along with disease-accelerating CCR5 variants had an even higher risk of HIV acquisition and rate of progression to AIDS.

Impact of Genetic Variation

"This work adds significantly to our understanding of the central role that molecules that interact with the CCR5 co-receptor play in influencing susceptibility to HIV/AIDS," says Carl W. Dieffenbach, Ph.D., who oversees basic research at NIAID's Division of AIDS.

"In addition, by examining the duplication of a specific gene, this study further emphasizes the significance of defining all existing types of genetic variation and the impact that these variations may have on human susceptibility to infectious diseases," Dr. Dieffenbach notes.