Genetic determinants of Kawasaki disease version 1

  • Research type

    Research Study

  • Full title

    Genetic determinants of Kawasaki disease for susceptibility and outcome

  • IRAS ID

    115933

  • Contact name

    Michael Levin

  • Contact email

    m.levin@imperial.ac.uk

  • Sponsor organisation

    Imperial College

  • Research summary

    Summary of Research:
    Introduction Kawasaki disease remains the commonest cause of acquired cardiac damage in children. There is an increasing awareness of the importance of this condition amongst paediatricians, particularly in those who manage children presenting with fever to healthcare settings, including primary care and emergency departments. It is a condition that requires rapid recognition and urgent targeted treatment with specialist medicines that help reset the immune system.
    Major questions in Kawasaki disease that remain unanswered are why do some children get Kawasaki disease and not others? And, in the absence of any accurate diagnostic test, how can we better diagnose it quickly so that we can start treatment promptly?

    Genetic predisposition
    There is strong evidence that inherited genetic factors play an important role in susceptibility to Kawasaki disease. This genetic predisposition goes someway to explain the highly variable incidence of Kawasaki disease in different parts of the world; for instance it is more common in Japan. But it is unknown whether a genetic predisposition may also explain why some children develop more severe damage to the coronary arteries (called coronary artery aneurysms), whereas other children appear to have no damage after Kawasaki disease.

    The UK Kawasaki Genetics study investigated the diagnosis and genetic predisposition in Kawasaki disease. It was an observational study, with two arms. In the retrospective arm, we identified patients with a history of previous Kawasaki disease, working with the UK Kawasaki Support Group. By collecting saliva samples from the study participants, and extracting their DNA, we investigated whether we could find genetic changes that increased the risk of coronary artery aneurysms. We did this by looking at genetic variation across the entire genome of 200 cases, and combining this with existing, published data. In a study published in the European Journal of Human Genetics in 2021, we confirmed data from Europe and Japan that identified changes in genes that are associated with Kawasaki disease. But we also discovered a new change on chromosome 20q13 where particular pattern of genetic sequence was strongly associated with increased risk of patients developing coronary artery aneurysms.

    Diagnosis of Kawasaki disease
    In the prospective arm of the study, we recruited new patients presenting with Kawasaki disease in a range of hospitals across the UK, and we collected research samples at the first time after a diagnosis of Kawasaki disease was first made. These samples are valuable for research into the biology behind Kawasaki disease, including identifying the potential causes of Kawasaki disease, and development of diagnostic tests for Kawasaki disease. We have used these samples to continue our development of a diagnostic test that could identify Kawasaki disease from a blood sample, based on the pattern of genes switched on or off in the sample. Using these samples, we have tested a new approach that would measure the likelihood of Kawasaki disease alongside the likelihood of other similar conditions – including bacterial and viral infection – so that a child with fever could have a blood test to determine whether Kawasaki disease or something else was causing their illness. These results have been submitted for publication.

  • REC name

    London - Fulham Research Ethics Committee

  • REC reference

    13/LO/0026

  • Date of REC Opinion

    25 Feb 2013

  • REC opinion

    Further Information Favourable Opinion