Psoriasis Genes: How genetics point to individualized solutions

The National Psoriasis Foundation estimates that about 7.5 million people in the US have psoriasis. There is a strong genetic component to psoriasis, and it tends to run in families. Along with the skin condition, other autoimmune conditions, such as Crohn’s disease, psoriatic arthritis, and uveitis, can be found more often in people with psoriasis.[ref][ref]

What causes psoriasis?

Psoriasis is an autoimmune condition that causes dry, sometimes itchy patches of skin. The immune system attacks the skin cells causing a speed-up in the turnover of the cells.

Human skin cells are in constant motion of shedding older cells and replacing them with new skin cells about once a month. However, for people with psoriasis, the turnover rate for skin cells can be as fast as three to four days, with the dead cells building up and flaking off in itchy, dry patches.[ref]

HLA genes and psoriasis:

The HLA genes code for proteins that are a big part of our immune system, known as the major histocompatibility complex(MHC), which helps the body identify foreign invaders. There are six different HLA class I genes (A, B, C, E, F, and G) and five different HLA class II genes (DM, DO, DQ, DP, and DR). (Here is a good video on the HLA family for those who want to learn more.)

There are a lot of genetic differences within the HLA genes leading to some people being more susceptible to one thing along with being less susceptible to something else.

Tradeoffs: The variability of HLA genes is a tradeoff that keeps our population as a whole thriving — some of us are great at fighting off a herpes virus while others are less susceptible to getting tuberculosis or leprosy.

In fact, some researchers hypothesize that the HLA type susceptible to psoriasis is prevalent in humans because it is preventative for leprosy.[ref]

Different HLA genes are often associated with autoimmune diseases. For example, HLA-DQ2 is implicated in susceptibility to celiac disease (check your genes here), and HLA-B27 is tied to several different autoimmune diseases (check your genes here).

Susceptibility to psoriasis is linked to a couple of HLA genes. Just carrying the HLA type is not enough to cause psoriasis by itself, so the genetic variants act together with other genes or environmental factors to cause psoriasis.

Lifehacks:

Will Biologics Work for You?

Certain psoriasis medications work better for people with certain HLA types. You may want to talk with your doctor about your genetic information and the research studies showing which medications may work best. A recent study (full study –take to your doc) shows the type of psoriasis medication known as biologics works better for those who carry the HLA-Cw*0602 serotype. Although the study only included a few hundred people, a couple of the biologics were clearly more likely to be effective based on HLA type.

Breaking this down even further, the type of biologic that is an anti-TNF-alpha drug was found in a study to be more likely to be effective in those who carry the rs1799724 C/C genotype (TNF -857C).[ref]

TNF-alpha gene:

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Updated and expanded on 11/04/2019