Identifying the genes involved in a disease can reveal insights into its causes and aid in the development of new treatments, but such studies need thousands of individuals. These numbers are difficult to achieve in IgA nephropathy.
Although more common than other types of immune-related nephropathy, IgA nephropathy is difficult to diagnose and also difficult to detect in verified patients. “The diagnosis requires a kidney biopsy, which is an invasive procedure that carries a lot of risk,” explains Krzysztof Kiryluk, MD, associate professor of medicine at Columbia University’s Vagelos College of Physicians and Surgeons. , so the diagnosis is often missed”. of research.
Kiryluk and his colleagues overcame the numerical challenge by assembling an extensive network of partners including nephrologists, geneticists and other scientists from four continents. Each participant gathered patients who had biopsies in their area and delivered blood samples to the Kiryluk’s Columbia team for DNA extraction and analysis.
The researchers compared DNA from people with IgA nephropathy with DNA from people without the disease using samples from more than 40,000 people. The 10-year study, which involved more than 200 scientists and clinicians from more than 100 institutions, is the largest-ever study on the genetics of IgA nephropathy.
Genetic exploration and potential therapeutic targets in IgA . nephropathy
Many of the new genes discovered in the study are involved in the production of IgA antibodies, giving credence to the notion that regulation of IgA levels is an important role in this disease.
“It’s a very important finding because IgA nephropathy is considered a kidney disease, but it seems that its origin lies outside of the kidney,” says Kiryluk. “We have also developed a genetic risk profile that can help identify patients who are most at risk of progressing to kidney failure,” said Ali Gharavi, MD, Jay Meltzer, MD, Professor of Nephrology and Growth. blood pressure and co-leader of the study.
The researchers also identified proteins produced by newly discovered genes that appear to be the biggest drug development targets. They also found two drugs that had previously been tested for different diseases and may have potential as IgA nephropathy therapy.
“A recent analysis shows that drug targets supported by genetic studies are more likely to succeed, and we expect that pharmaceutical companies will begin to develop new therapies,” says Kiryluk. new method based on our findings”.
Authority to solve:
- Genome-wide association analyzes identify pathogenic signaling pathways and prioritize drug targets for IgA nephropathy – (https://pubmed.ncbi.nlm.nih.gov/37337107/)