VARIATION in the copy numbers of a gene involved in the innate immune system has been associated with an increased risk of the immunoglobulin A (IgA) nephropathy kidney disease.
Researchers have found that the number of copies of the alpha-defensin gene is a significantly linked with IgA nephropathy, although it remains unclear how the gene is directly involved in the development of the disease. One member of the research team, Prof John Armour, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK, said: “The data overwhelmingly support the association, but we still do not understand what the connection might be between alpha-defensins and molecular events that cause the kidney problems.”
IgA nephropathy, also known as Berger’s disease, involves IgA settling in the kidney and causing scarring and inflammation. High blood pressure, swollen ankles, and high levels of cholesterol also characterise the disease. In the most extreme cases it can lead to kidney failure. Previous studies have indicated that a predisposition to the disease is caused by genetic factors. To further explore this link, Prof Armour and the research team measured genetic variation in >1,000 patients with IgA nephropathy and compared them with >1,000 controls.
A significant difference in the number of alpha-defensin genes was found between the two groups. The researchers concluded that the strongest genetic factor in the onset of the disease was the variation in the number of these genes, which produce proteins that kill bacteria as part of the innate immune system. The findings of the research do not suggest obvious new therapies for the disorder. However, the researchers hope that these findings will improve the likelihood of identifying those who are most at risk of the kidney disease. It will also provide a new pathway for investigation into the impact of alpha-defensin gene copy numbers on the development of kidney disease.