Strong genetic risk factor for kidney disease may lead to new treatment target
A strong genetic risk factor for IgA nephropathy (IgAN) and related renal dysfunction has been discovered by an international research team. This discovery has advanced the researchers’ understanding of the most common inflammatory kidney disease worldwide.
Asia has a higher prevalence of IgAN compared to Western countries with 15-40% of the patients eventually progressing to end-stage renal diseases within 20 years of the disease onset.
The team investigated copy number variations (CNVs) of the alpha-defensin gene in Chinese patients with IgAN and healthy controls as well as a Caucasian cohort with IgAN. They found that a low copy number of the alpha-defensin gene increases the risk of IgAN, and the CNV of alpha-defensin gene can explain the 4.96% of disease risk.
“As a major source of genetic variation, CNVs have long been suggested to play important roles in disease development, but only a few specific CNVs have demonstrated convincing evidence. This CNV contributes more genetic risk to IgAN than the cumulative effect of all the other loci we have discovered. So, this discovery is truly exciting,” said Professor LiuJianjun, lead author of the study as well as Deputy Director for Research Programmes and Senior Group Leader of Human Genetics at A*STAR’s Genome Institute of Singapore (GIS).
In addition, the researchers also found that the low copy number of the alpha-defensin gene also increases the risk of renal dysfunction in IgAN patients. This is the first study that demonstrates the vital role of alpha-defensin gene in IgAN development and related renal dysfunction, suggesting the gene to be a potential therapeutic target for this important kidney disease.
“The discovery of IgAN susceptibility gene, alpha-defensin, is a major breakthrough in the fight against the disease. It will pave the way for identifying individuals at high risk for IgAN. It may also reveal new treatment target (i.e. its protein product – human neutrophil peptides) to prevent the onset and progression of IgAN,” said Dr. Lim Su Chi, Clinical Director, Clinical Research Unit at the Khoo Teck Puat Hospital.
The study was also led by Prof Yu Xueqing, Professor of Medicine and Director of the Institute of Nephrology at the First Affiliated Hospital of Sun Yat-sen University (SYSU), and the current President of the Chinese Society of Nephrology.
To date, the collaborative research team from GIS and SYSU have already discovered five novel genetic risk loci for IgAN.
