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 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 in causing psoriasis.
Genetic Variants Associated with Psoriasis
Over 60% of psoriasis patients carry a specific HLA variant called HLA-Cw*0602. This variant is found in about 10% of the population. 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: typical risk of psoriasis
- C/T: increased risk of psoriasis
- T/T: a large increase in the risk of psoriasis[ref]
Members: Your genotype for rs10484554 is —.
Check your genetic data for rs1265181 (23andMe v4, v5 ; AncestryDNA):
- G/G: typical risk of psoriasis
- C/G: increased risk of psoriasis
- C/C: increased risk of psoriasis* [ref][ref]
Members: Your genotype for rs1265181 is —.
*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]
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: typical
Members: Your genotype for rs2395029 is —.
IL23 gene: codes for interleukin-23, a component of the immune system
Check your genetic data for rs11209026 (23andMe v4, v5; AncestryDNA):
- G/G: most common genotype, higher risk of psoriasis[ref]
- A/G: ~50% decreased risk of psoriasis
- A/A: ~50% decreased risk of psoriasis
Members: Your genotype for rs11209026 is —.
PTPN22 gene: helps code for the protein PTP (protein tyrosine phosphatase) and PTP helps control the activity of T cells.
Check your genetic data for rs1217414 (23andMe v4; AncestryDNA):
- A/A: increased risk of psoriasis[ref]
- A/G: typical risk of psoriasis
- G/G: typical risk of psoriasis
Members: Your genotype for rs1217414 is —.
near the IL12B gene: encodes interleukin 12 beta
Check your genetic data for rs4085613 (23andMe v4, v5; AncestryDNA):
- G/G: typical
- G/T: increased risk of psoriasis
- T/T: increased risk of psoriasis[ref]
Members: Your genotype for rs4085613 is —.
Will Biologics Work for You?
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 –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]
Check your genetic data for rs1799724 (23andMe v4, v5):
- C/C: biologic (etanercept), anti-TNFalpha more likely to be effective[ref]
- C/T: a greater chance that anti-TNFalpha won’t be effective
- T/T: a greater chance that anti-TNFalpha won’t be effective
Members: Your genotype for rs1799724 is —.
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.[ref]
Check your genetic data for rs1061622 (23andMe v4, v5; AncestryDNA):
- T/T: etanercept (Enbrel), anti-TNFalpha more likely to be effective[ref]
- G/T: a greater chance that anti-TNFalpha won’t be effective
- G/G: a greater chance that anti-TNFalpha won’t be effective
Members: Your genotype for rs1061622 is —.
Another study found other TNF-alpha variants could also be used to help predict who would respond well to anti-TNFalpha biologics.[ref]
Check your genetic data for rs1800629 (23andMe v4, v5; AncestryDNA):
- A/A: higher TNF-alpha levels,
- A/G: higher TNF-alpha levels –
- G/G: typical, better response to etanercept and anti-TNFalpha medications[ref]
Members: Your genotype for rs1800629 is —.
Check your genetic data for rs361525 (23andMe v4, v5; AncestryDNA):
Talk with your doctor, of course, on which medicine is best for your situation.
Blueprint for Members:
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Updated and expanded on 11/04/2019