APolipoprotein L1 in People of african ancestry Living in the UK: Exploration of genetic and environmental factors associated with Chronic Kidney Disease
King's College London
Duration of Study in the UK
3 years, 0 months, 1 days
People of African ancestry have 3-5 fold higher rates of chronic kidney disease (CKD). Mutations in the Apolipoprotein-L1 gene are present in many people of African ancestry with CKD and appear to protect against sleeping-sickness. However, some people have these mutations, but do not have kidney disease. We plan to recruit 500 patients of African ancestry with kidney disease (including 100 patients who have previously had kidney biopsies) and 100 African ancestry healthy controls, and use material from deceased black donors without kidney disease from the Quality in Organ Donation (QUOD)biobank.
We propose to compare molecular changes in specific parts of APOL1 genes which may lead them being ‘switched-on’ in blood/spleen, kidney and urine (if available from cases) samples from 100 CKD patients and 100 QUOD deceased kidney donor controls. This will help us to understand if blood or urine samples give us the same information as kidney tissue about these genetic changes, and how the genetic changes affect disease development.
We also think that secondary 'triggers' may affect disease development in people with APOL1 mutations which are likely to include infection or inflammation. We will also compare inflammatory factors in blood and urine between participants with CKD and controls.
Finally, we will develop 'inducible pluripotent stem cells' from the blood cells of 18 participants (9 CKD and 9 controls with specific APOL1 mutations). These cells will be used to grow kidney cells and we will see how the APOL1 mutations affect cell development and their response to inflammation.
The findings will help us to understand how APOL1 disease develops and may identify people with APOL1 mutations at risk of CKD.
North West - Greater Manchester West Research Ethics Committee
Date of REC Opinion
3 May 2022
Further Information Favourable Opinion