SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.
A gene variant found mainly in people with African ancestry increases the odds of HIV infection in African Americans exposed to the virus says a study published today. Once infection has set in, however, this same variant slows the progression of the disease, allowing people to live about two years longer.
The authors of the study, published today in Cell Host & Microbe, estimate that in Africa, this genetic variant may be responsible for 11% of the HIV burden.
In a cohort of close to 1,300 African Americans, He et al. found that those people who lacked a protein on their red blood cells called the Duffy antigen had 40% higher odds of being infected by HIV but were more likely to have a slower progression of their disease.
About 90% of sub-Saharan Africans, and close to 70% of African Americans, are “Duffy negative,” meaning they have two copies of a particular version of the Duffy antigen gene that prevents the protein from being made in red blood cells. Duffy negativity has previously been associated with resistance to one strain of malaria, Plasmodium vivax.
“After thousand of years of adaptation, this Duffy variant rose to high frequency because it helped protect against malaria,” said Matthew Dolan, one of the study’s authors. “Now, with another global pandemic on the scene, the same variant renders people more susceptible to HIV. It shows that complex interplay between historically important diseases and susceptibility in contemporary times.”
The slowing of disease progression seen in Duffy-negative HIV-positive individuals was comparable to that seen in Europeans who carry a genetic variant called “CCR5Delta32”. Two copies of CCR5Delta32 render people resistant to the most common strain of HIV, while having just one copy is associated slowed disease progression.
(23andMe customers can see their data for the Duffy antigen, CCR5Delta32, and other SNPs mentioned here at the end of this post.)
The authors of the current study speculate that the seemingly contradictory effect of the Duffy antigen on HIV – lacking the protein promotes infection but slows disease — are due to complex interactions between the Duffy antigen and chemicals called chemokines that bind to it and the HIV virus itself. They propose a model in which being Duffy-positive results in increased anti-HIV chemokines in the bloodstream, which helps fight off an HIV infection. But in the event the virus does get a foothold, the increased chemokines actually facilitate disease progression by increasing inflammation, and the Duffy antigen ends up being a liability by providing a binding site for the HIV virus.
“The parts of a car that get it into gear are separate from those that get it moving once in gear,” said Sunil Ahuja, senior author of the paper. “ A similar analogy applies to HIV; the factors that influence its transmission are not necessarily the same as those that influence disease progression.”
The results of the current study not only suggest that Duffy-negativity might be an important part of the picture when considering the global HIV pandemic; they also help explain previous studies, which showed genetic variants that increase the levels of two chemokines in particular – CCL2 and CCL5 – were associated with faster disease progression in European Americans.
The authors of the current study found that those other variants also accelerate disease progression among African Americans – but only among those who are Duffy positive. Among the majority of African Americans who are Duffy negative, the genes affecting CCL2 and CCL5 appear to make little difference. In their conclusion, the researchers point out that these results demonstrate the importance of understanding the interactions between genes that affect disease susceptibility.
If you are a 23andMe customer, you can use the links and tables below to check your data for each of the SNPs mentioned in this post.
(this is the same SNP used in the 23andMe My Gene Journal (now called Health and Traits) article on Malaria Resistance)
|CC||Duffy-negative: increased odds of HIV infection upon exposure, but slowed disease progression if infected|
23andMe custom SNP i3003626
|II||+/+: Not resistant to HIV infection; shows average time of progression to AIDS after infection.|
|DI||Delta32/+: Not resistant to HIV infection but may have slower progression to AIDS after infection.|
|DD||Delta32/Delta32: Resistant to infection by the most common strain of HIV people usually encounter, though protection is not complete.|
|AA||Typical CCL2 levels; no effect on HIV|
|AG||Typical CCL2 levels; no effect on HIV|
|GG||Increased CCL2 levels; increased rate of disease progression|
|CC||Typical CCL5 levels; no effect on HIV|
|CT||Typical CCL5 levels; no effect on HIV|
|TT||Increased CCL5 levels; increased rate of HIV disease progression|
If you’re really interested, here are links to the original CCL2 and CCL5 studies that found that the SNPs detailed above increased the levels of these chemokines and the rate of disease progression in HIV infected European Americans.