Wednesday, July 16, 2008

Another tradeoff in order to avoid malaria?

Genetic trait boosts AIDS risks in Blacks in Yahoo! News. Unfortunately, I don't have access to the full text of this paper. It looks really good, uses access to a large sample, and shows biological effects of genetic variants.
I assume and hope that they control for population stratification when they find that the "DARC −46C/C is associated with 40% increase in the odds of acquiring HIV-1"

Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS Susceptibility
Weijing He, Stuart Neil, Hemant Kulkarni, Edward Wright, Brian K. Agan, Vincent C. Marconi, Matthew J. Dolan, Robin A. Weiss, and Sunil K. Ahuja
Cell Host and Microbe Volume 4, Issue 1, 17 July 2008, Pages 52-62
Abstract: Duffy antigen receptor for chemokines (DARC) expressed on red blood cells (RBCs) influences plasma levels of HIV-1-suppressive and proinflammatory chemokines such as CCL5/RANTES. DARC is also the RBC receptor for Plasmodium vivax. Africans with DARC −46C/C genotype, which confers a DARC-negative phenotype, are resistant to vivax malaria. Here, we show that HIV-1 attaches to RBCs via DARC, effecting trans-infection of target cells. In African Americans, DARC −46C/C is associated with 40% increase in the odds of acquiring HIV-1. If extrapolated to Africans, 11% of the HIV-1 burden in Africa may be linked to this genotype. After infection occurs, however, DARC-negative RBC status is associated with slower disease progression. Furthermore, the disease-accelerating effect of a previously described CCL5 polymorphism is evident only in DARC-expressing and not in DARC-negative HIV-infected individuals. Thus, DARC influences HIV/AIDS susceptibility by mediating trans-infection of HIV-1 and by affecting both chemokine-HIV interactions and chemokine-driven inflammation.


Bob said...

Have you seen p-ter's criticism of this work over at GNXP (Classic)?

Yann Klimentidis said...

Yes, I did very briefly see that... pretty shocking if they really didn't control for pop. stratification!! I'll have to have a closer look at p-ter's post and the paper.

Bob said...

Ya, it seems poorly done to me, although I'm a novice just reading and trying to learn stuff.

Genetic Future has further complaints about the paper.

I don't know the field well (by which I mean "not at all"). Is this from a well-respected lab?


Yann Klimentidis said...

-don't know.

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