Psoriasis Genes

Itchy, painful, cracked skin that won’t go away… crumbling nails, inflamed scalp…. these are just some of the problems that people with psoriasis deal with every day.

The National Psoriasis Foundation estimates that about 7.5 million people in the US have psoriasis. There is a genetic component to psoriasis, and it tends to run in families. Along with the skin condition, there are other autoimmune conditions, such as Crohn’s disease, psoriatic arthritis, and uveitis, that are 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. It is caused by the immune system attacking your skin cells, speeding up the turnover of the cells. Everyone’s skin cells are constantly being replaced; normally skin cells are being replaced about once a month. 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 four different HLA class I 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, which leads to some people being more susceptible to one thing along with being less susceptible to something else.

This 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 hypothesize that the HLA type susceptible to psoriasis is prevalent in humans because it is preventative for leprosy.

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 in causing psoriasis.


Genetic Variants Associated with Psoriasis

HLA-C Gene

Over 60% of psoriasis patients carry a specific HLA variant called HLA-Cw*0602.  This variant is found in about 10% of the population as a whole. Therefore, just carrying the variant isn’t enough to cause psoriasis, but it does make a person much more susceptible to it.

A doctor (or lab) can do a test to see if you carry the HLA-Cw*0602 variant for sure, but there are a couple of variants of the HLA-C gene that are available through 23andMe and linked to significantly increased psoriasis risk.

Check your genetic data for rs10484554 (23andMe v4, v5; AncestryDNA):

  • C/C: normal risk of psoriasis
  • C/T: increased risk of psoriasis
  • T/T: increased risk of psoriasis[ref]

Check your rs1265181 (23andMe v4, v5; AncestryDNA):

  • G/G: normal risk of psoriasis
  • C/G: increased risk of psoriasis
  • C/C: increased risk of psoriasis, a Chinese study found 22x increased risk*[ref]

*Note that the orientation on this is flipped to match 23andMe (plus strand) orientation. If you are looking at the older studies on the SNP, you will see G as the risk allele (minus strand orientation).

Research studies show a connection between strep throat and psoriasis, which may be increased due to HLA-Cw*0602:

  • People with HLA-Cw*0602 are twice as likely to have a positive throat swab for streptococcus at the onset of psoriasis symptoms. [ref]
  • A small study found that people with two copies of the HLA-Cw*0602 serotype had a much greater improvement in their psoriasis after a tonsillectomy than those without the HLA-Cw type. [ref]

There is also a link between IBD and psoriasis.[ref]

HLA-B *5701:

A variant of the HCP5 gene predicts the HLA-B*5701 genotype for Caucasians and Hispanics with 99.9% accuracy.

Check your genetic data for rs2395029 (23andMe v4, v5; AncestryDNA):

  • G/G: very likely to be HLA-B*5701 homozygous, increased risk of psoriasis (and other autoimmune diseases)[ref][ref][ref]
  • G/T:  likely to carry one copy of HLA-B*5701, increased risk of psoriasis (and other autoimmune diseases)
  • T/T: normal

Lifehacks

Biologics:

Certain psoriasis medications work better for people with certain HLA types.  So take your genetic information to your doctor along with the research studies showing which medications may work best. A recent study (full study – .pdf for printing to take to your doc) show that 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). The same study found that those carrying the TNF receptor variant rs1061622 T/T genotype (TNFRSF1B 676T) were also more likely to have a good response to the anti-TNF-alpha biologic. The study was done using etanercept (Enbrel). Unfortunately, the study (Pharmacogenetic analysis of TNF, TNFRSF1A, and TNFRSF1B gene polymorphisms and prediction of response to anti-TNF therapy in psoriasis patients in the Greek population.) is only available in full behind a paywall, so you may need your doctor to get a copy of it.

Natural TNF-alpha reducers:

Natural options for treating psoriasis include quercetin and berberine (Oregon grape).  Quercetin has been shown in several mouse studies to reduce levels of TNF-alpha and NF-kappa beta. Berberine, found in several different plants including Oregon grape), has been shown to decrease psoriasis symptoms when used topically.[ref][ref]

 

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