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January 07, 2005

Genetic Factors in Determining HIV/AIDS Risk

Just spotted this press release over at the National Institute of Allergy and
Infectious Diseases (NIAID) site >>

Scientists Discover Key Genetic Factor in Determining HIV/AIDS Risk

“Individual risk of acquiring HIV and experiencing rapid disease progression is not uniform within populations,” says Anthony S. Fauci, M.D., director of 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, 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.”

The study focused on the gene that encodes CCL3L1, a potent HIV-blocking protein that interacts with CCR5—a major receptor protein that HIV uses as a doorway to enter and infect cells....

The researchers analyzed blood samples from more than 4,300 HIV-positive and -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- and Hispanic-American adults averaged two and three copies, respectively.

...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.

...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.”

The study is published over at Science Express: E Gonzalez et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science DOI: 10.1126/science.1101160.

Posted by theresa at 09:07 AM