Abstract: SA-PO395
Genetic Risk Factors in a United Kingdom Paediatric Nephrotic Syndrome Cohort
Session Information
- Genetic Diseases of the Kidney - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Platt, Caroline Jane, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
- Welsh, Gavin Iain, University of Bristol, Bristol, United Kingdom
- Koziell, Ania B., Kings College London, London, United Kingdom
- Saleem, Moin, University of Bristol, Bristol, United Kingdom
- Bierzynska, Agnieszka, University of Bristol, Bristol, United Kingdom
Background
Up to 30% of steroid resistant nephrotic syndrome (NS) patients have a genetic cause while the cause of the remaining group remains unknown. A yet unidentified ‘circulating factor’ (CF) has been attributed to the subset of patients who fail to respond to immunosuppression and in whom disease recurs post-transplant. There are emerging reports that apart from disease causing mutations in ‘nephrotic’ genes there are also common genetic variations in ‘susceptibility genes’ that may play important role in the development and/or disease progression of NS.
We aimed to validate and add to the published findings on genetic variations in ‘susceptibility genes’. We stratified patients into groups based on their clinical course and hypothesised that they may have different genetic ‘signatures’ in the selected genes.
Methods
We searched literature for previously published risk factor/modifier genes for NS/FSGS. We then screened the genes in 133 exome sequenced Caucasian patients with paediatric onset of NS. Phenotypic data was collected through a National Registry of Rare Kidney diseases. The frequency of detected single nucleotide variations (SNVs) in the cohort was compared with the ‘general population’. Chi-squared test with Yates correction (2x2 contingency tables) was used. Sub-group analyses were performed for genetic SRNS and the presumed CF patients.
Results
number of previously described SNVs were enriched in our cohort when compared to the general population. We have also found several other SNVs to be significantly over-represented, that were not described before and which may therefore, be involved in susceptibility to the disease in some way. The identification of these variants provides new avenues for further exploration. By stratifying NS patients in the case of HLA-DRB1 and HLA-DQA1 for example, we found a sub-set of variants that are specifically enriched in likely CF disease.
Conclusion
These results support and add to the hypothesis that there are a number of genetic variants (residing outside of the known ‘nephrotic’ genes) working alone or in combination, to modify the pathogenesis of NS.