Differences in the comorbidities experienced between HLA-C*06:02 carrier groups in 9,000 psoriasis patients

Psoriasis is a very common skin condition with major impact on health and wellbeing. Unfortunately, some people also develop other health conditions (often termed ‘comorbidities’) such as arthritis and heart disease.

A person’s genetic make-up is an important determinant factor of health and disease. We know very little about the genes that determine whether a person will develop psoriasis comorbidities, but we know more about the genes that can lead to psoriasis. Of these, a gene called HLA-C is by far the most important. People with a version of this gene known as HLA-C*06:02 are at considerably higher risk of developing psoriasis than people with other versions of HLA-C. We therefore set out to explore what influence HLA-C*06:02 has on risk for psoriasis comorbidities.

We used information on more than 9,000 people with psoriasis, collected through two UK studies, UK Biobank and BSTOP. This included medical and genetic information, made available to our researchers with participants’ consent. We divided the study participants into two groups: those who did, and those who did not carry the HLA-C*06:02 version of the HLA-C gene. We then compared comorbidities and other health-related outcomes between these two groups.

Our study confirmed that people who carry HLA-C*06:02 are more likely to have psoriasis earlier in life. While the differences between groups were not large, we found a definite tendency for people without HLA-C*06:02 to be above a healthy weight, and to suffer more heart problems. We also found this to be more evident in women than in men. It may be that HLA-C*06:02 in some way protects people with psoriasis against development of certain comorbidities, compared to other versions of the HLA-C gene. Or perhaps people who don’t carry HLA-C*06:02 carry other genes that increase their risk of comorbidities.

These results are only the first step in understanding why some people with psoriasis develop comorbidities and some do not. It does however provide an important direction for future research. We need to further investigate the differences between men and women across other genes to understand how they might play a role in development of comorbidities. Testing for HLA-C*06:02 status alone won’t be powerful enough to identify everyone at risk of comorbidities but might be helpful if combined with other risk factors.

Related publication
Differences in clinical features and comorbid burden between HLA-C*06:02 carrier groups in more than 9,000 people with psoriasis
Konstantinos Douroudis, Ravi Ramessur, Ines A. Barbosa, David Baudry, Michael Duckworth, Caroline Angit, Francesca Capon, Raymond Chung, Charles J. Curtis, Paola Di Meglio, Jonathan MR. Goulding, Christopher EM. Griffiths, Sang Hyuck Lee, Satveer K. Mahil, Richard Parslew, Nick J. Reynolds, Alexa R. Shipman, Richard B. Warren, Zenas ZN. Yiu, BADBIR Study Group, BSTOP Study Group, Michael A. Simpson, Jonathan N. Barker, Nick Dand, Catherine H. Smith
doi: 10.1016/j.jid.2021.08.446