Thursday, January 06, 2005

CCL3L1: Genetic Factor in Determining HIV/AIDS Risk

Researchers have reported finding a genetic factor that influences the risk of HIV/AIDS.  The effect is twofold: it alters the risk of contracting HIV infection; and it alters the risk that HIV with progress to AIDS in a given period of time.  The factor that was studied turns out to be a subtle one.  The human genome contains a gene called CCL3L1.  A person can have more than one copy of this gene.  The more copies, the lower the risk. 

The study was reported on Science Express, the online version of Science Magazine that is used for early reporting of important findings, before the print version comes out.  I don't have a subscription, which is required, even to view the abstract.  However, there are reports on News@Nature.com and on the NIH website.  From the NIH report:
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 senior authors 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.

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.

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.
The Nature report adds some background.  The author explains more about the role of CCR5, and the interactions between the CCL3L1 protein and the CCR5 receptor.  She also reports on an interview with a geneticist, Mary Carrington.  Dr. Carrington talks about the potential clinical application of the findings.  Patients could be advised to follow a more aggressive medication regimen, if their genetic disposition puts them at higher risk.  Also interviewed was a infectious disease specialist, Michael Lederman.  Dr. Lederman points out that patients in clinical trials for HIV vaccines could be divided into groups based upon their genetic makeup.  This could help researchers find out who is most likely to respond to a vaccine. 

Although the clinical applications are not great, at this point, the HIV/AIDS problem is so great, that any finding is welcome. 

An interesting aspect of the study is that the variation in CCR5 and CCL3L1 together account for about 40% of the variance in the risk of HIV infection.  That means, of course, that there are other factors, perhaps more important, that remain to be elucidated.