Using genetics to change the way both patients and doctors manage psoriasis

I am immensely appreciative to the British Skin Foundation (BSF) for supporting my research fellowship at the St John’s Institute of Dermatology. As a dermatology registrar, I value being able to take time out of my clinical training to work with leading academic dermatologists and genetics experts on this exciting project. I am learning a vast array of skills, which I hope to carry forward in my future research career. I am also grateful for the support of my supervisors, Dr Satveer Mahil, Dr Nick Dand and Professor Catherine Smith (St John’s Institute of Dermatology), as well as the genetics department at King’s College London.  I would also like to thank our external collaborators: Dr Kayleigh Mason (University of Manchester) and Dr Ashley Budu-Aggrey (University of Bristol).

Images in order: Dr Ravi Ramessur, Dr Satveer Mahil, Dr Nick Dand, Professor Catherine Smith, Dr Kayleigh Mason and Dr Ashley Budu-Aggrey.

Psoriasis is common, affecting around 2 in every 100 people. In this condition, skin cells grow and shed more rapidly than usual. People with psoriasis may have red scaly patches of skin that they find itchy, painful and embarrassing. This hugely affects quality of life – sometimes even as much as having heart disease or cancer. People with psoriasis are also more likely to suffer from other health problems beyond the skin including joint disease, obesity and depression.

Metabolic syndrome is a common cluster of conditions that occur together, significantly increasing the risk of heart disease and stroke in those affected. It affects approximately 1 in 3 people over the age of 50 in the UK. Individuals are diagnosed with metabolic syndrome if they have from 3 or more of the following component conditions:

• Excess body fat around the waist (increased waist circumference)
• Abnormal blood cholesterol or lipid levels
• High blood sugar levels
• High blood pressure

People who suffer from psoriasis have been found to be over two times more likely to have metabolic syndrome. Additionally, it has been shown that people with more severe psoriasis have an even greater chance of also suffering from metabolic syndrome than those with mild psoriasis. It is unclear whether metabolic syndrome directly causes a worsening of psoriasis or vice versa. Furthermore, it is not known whether any of the component conditions of metabolic syndrome drives the onset of psoriasis and if so, whether this effect is additive in those who suffer from more than one component trait.

Our study will use a powerful genetic technique called Mendelian randomisation to determine whether metabolic syndrome, or its component conditions, directly cause psoriasis. Mendelian randomisation uses the naturally occurring, random genetic variation between individuals in a population to unpick whether a particular risk factor causes a condition.

We will use information from previous studies where both genetic samples and clinical measurements have been taken from thousands of individuals from the general population.

We aim to uncover:

• Whether metabolic syndrome directly causes psoriasis (and vice versa)
• Whether each component of metabolic syndrome directly causes psoriasis (and vice versa)
• Whether the effects of any of the component conditions are additive in their propensity to drive psoriasis

The results of this project have the potential to change the way both patients and doctors manage psoriasis by shifting the focus from skin only aspects of disease. If metabolic syndrome is shown to directly cause psoriasis, then it would be important to address many of its modifiable component conditions. Treating these would potentially not only improve psoriasis but also the general health of the large number of people with psoriasis who also suffer from metabolic syndrome.

The results of this project will help to contribute to an application for PhD funding in order to enable us to further investigate potential mechanisms through which metabolic syndrome (or any of its component traits) may be driving psoriasis.  Targeting these mechanisms with medications may be more effective than conventional treatments in patients who suffer from psoriasis and metabolic syndrome.

Dr Ravi Ramessur, St John’s Institute of Dermatology