Studies suggest psoriasis may have had an evolutionary purpose
Psoriasis often runs in families, and research continues to flesh out our understanding of the key role played by genetics in psoriasis and psoriatic arthritis. To date, researchers have identified more than 30 regions of the human genome where variations among individuals are linked to varying degrees of risk for developing psoriasis. Recent work led by Dr. Wilson Liao at the University of California, San Francisco suggests that some variations associated with increased risk for psoriasis may lend a clue to the challenges faced by our ancestors hundreds or thousands of years ago.
Our genomes are chains of DNA base-pairs, more than 3.5 billion of which are tethered together in our own very specific sequence. At the level of our DNA sequences, we differ from one another by only about 0.1 percent. But 0.1 percent of 3.5 billion is still 3.5 million differences—or polymorphisms—in our DNA sequences. Like the rest of our genome, these polymorphisms are passed with high fidelity from one generation to the next.
Liao's laboratory and those of his many collaborators have been examining our genomes for single-nucleotide polymorphisms (SNPs, often pronounced "snips"), or differences, in our DNA. The Human Genome Project of the 1990s laid the groundwork for identifying the millions of SNPs scattered throughout our genomes. These SNPs now serve as readily accessible genetic signposts that investigators can use to track associations between our health and the DNA sequences of our genomes.
Liao's most recent study builds on two earlier studies that revealed intriguing connections between specific SNPs and the risk for developing psoriasis. The experimental approach of the earlier studies involved comparing thousands of SNPs among hundreds of people with psoriasis with the same SNPs in many people without psoriasis. In a very few cases, SNPs from the psoriasis group were very different from those seen in the group without psoriasis. Interestingly, these SNPs often fell in regions of the genome associated with our immune system.
Researchers in one of the earlier studies noticed that at least one of the genetic variations associated with an increased risk for psoriasis had previously been associated with a decreased risk of developing Acquired Immune Deficiency Syndrome (AIDS) after HIV infection. Liao and his coworkers have followed up on this observation by combining data from the two previous studies and compared that data with those from similar studies of individuals infected with HIV. The results: Psoriasis patients indeed are often carrying genetic variations associated with better responses to HIV infection, such as fewer viruses in infected individuals and delays in developing AIDS. Why might this be?
We inherit the DNA sequences of our genomes from our parents who, in turn, received their DNA from their parents. The fact that our parents and their parents—and all direct ancestors before them—survived long enough to have children reflects the fact that they were biologically equipped to survive in their contemporary environment. In other words, our DNA is literally a testament to the successful circumstances under which our ancestors lived and had children in the past. In the case of genetic variations that predispose some of us to have psoriasis, at least some of these variations may be with us because of their success in combatting one or more viral infections. Given that HIV is likely to have arisen only within the last 60 or so years, the association between control of HIV infection and risk of psoriasis seen by Liao and his coworkers probably reflects a much older encounter between our ancestors and another, yet similar, deadly virus. Beyond providing fascinating genealogical insight, the work led by Liao identifies additional points in the immune system where treatment could stymie the immunological events that contribute to psoriasis.
Andrew D. Robertson, Ph.D., is the chief scientific and medical officer for the National Psoriasis Foundation.