Study finds genetic clues to major cause of kidney disease worldwide

April 5, 2011, National Institutes of Health

( -- For the first time, researchers have found five regions in the human genome that increase susceptibility to immunoglobulin A (IgA) nephropathy, a major cause of kidney failure worldwide — systematically identifying those that point to a tendency for IgA nephropathy, or a protection against it.

"The study is unique in identifying the biological pathways that mediate IgA nephropathy, mapping the way for further study that may reveal practical targets for diagnosis and treatment," said Dr. Ali Gharavi, Division of Nephrology at Columbia University in New York City, the principal investigator. 

"The cause and development of IgA nephropathy is poorly understood. Many biological pathways have been suggested, but none has been conclusive until now," he said. 

The ongoing genome-wide association study is funded by the National Institutes of Health’s Office of the Director, National Institute of Diabetes and Digestive and Diseases (NIDDK) and National Center for Research Resources, under an NIH Challenge Grant. The project is a part of the $10.4 billion provided to NIH through the Recovery Act. Results were published in the April issue of Nature Genetics.

Researchers looked at the genes of 3,144 people of Chinese and European ancestry, all of whom have IgA nephropathy. The disease occurs when abnormal IgA antibodies deposit on the delicate filtering portion of the kidney and form tangles. The immune system tries to get rid of the tangles, but the kidneys are caught in the crossfire, further destroying the delicate filters.

Worldwide prevalence of IgA nephropathy appears highest in Asia and southern Europe, and is responsible for most cases of in those populations. The U.S. prevalence is much lower — up to 10 percent, although Native Americans from New Mexico have reported rates as high as 38 percent.

"IgA nephropathy is most common in Asia, intermediate in prevalence in Europeans and rare in Africans. We found that the frequency of genetic risk variants was similarly highest in Chinese people, intermediate in Europeans and lowest in Africans. This suggests that their higher frequency in Asians may in part account for increased prevalence in this population," said Gharavi.

"Genetics are helpful if they tell you a story about the biology of disease. Here, we're seeing a story unfold about the precise immune basis of IgA nephropathy, which also appears to be genetically associated with other rare kidney diseases — connections that were previously unsuspected," said Dr. Rebekah Rasooly, an NIDDK scientist. "The beauty is that nobody had been looking in this direction, and now they are."

Some of the genes implicated in the study are especially interesting because they play a role in other (not kidney-related) immune disorders. For example, the complement factor H region, called a locus, has been associated with macular degeneration, a progressive eye disease that can result in blindness; and susceptibility to meningococcal infection, the bacteria that causes meningitis.

Rasooly noted that since the genes identified in the Asian population were also found in North American and Mediterranean European populations, this suggests the genetic basis for the disease is similar in these populations. "It’s possible that this research might be relevant to all populations," she said. "The study is also a great opportunity to conduct meaningful research with Recovery Act funding. Thanks to an NIH Challenge Grant, we now have a small but growing portfolio in this area, whereas we had nothing on it just a few years ago."

IgA nephropathy appears to be a benign disease in some people, causing only occasional blood in the urine, while others need a kidney transplant, according to Dr. Marva Moxey-Mims, a pediatric kidney specialist at NIDDK.

"What's the difference between these groups of people? This study begins to answer that question," she said. "Although these gene locations by themselves do not unequivocally predict individual risk for disease or severity of it, now we can do more specific, prospective clinical studies to determine if they have predictive power about clinical outcomes in IgA nephropathy."

Moxey-Mims added that the study also may one day point the way to a more accurate, less invasive way of diagnosing IgA nephropathy. Current diagnostic methods require a kidney biopsy, an invasive procedure that must be performed in a hospital.

The findings resulted from long-term collaborations among investigators in the United States, Italy and China. "This worldwide collaboration was critical to achieve sufficient momentum for the study and make progress in the field," said Gharavi. He and study co-principal investigator, Dr. Richard Lifton at Yale University in New Haven, Conn., will recruit another 5,000 patients worldwide.

More information: For additional information on IgA Nephropathy, please visit … ephropathy/index.htm

Related Stories

Recommended for you

Study of smoking and genetics illuminates complexities of blood pressure

February 15, 2018
Analyzing the genetics and smoking habits of more than half a million people has shed new light on the complexities of controlling blood pressure, according to a study led by researchers at Washington University School of ...

New mutation linked to ovarian cancer can be passed down through dad

February 15, 2018
A newly identified mutation, passed down through the X-chromosome, is linked to earlier onset of ovarian cancer in women and prostate cancer in father and sons. Kunle Odunsi, Kevin H. Eng and colleagues at Roswell Park Comprehensive ...

A gene that increases the risk of pancreatic cancer controls inflammation in normal tissue

February 14, 2018
Inflammation is a defensive response of the body to pathogens, but when it persists, it can be harmful, even leading to cancer. Hence, it is crucial to understand the relationship between inflammation and cancer. A group ...

Scientists develop low-cost way to build gene sequences

February 13, 2018
A new technique pioneered by UCLA researchers could enable scientists in any typical biochemistry laboratory to make their own gene sequences for only about $2 per gene. Researchers now generally buy gene sequences from commercial ...

New insights into gene underlying circadian rhythms

February 13, 2018
A genetic modification in a "clock gene" that influences circadian rhythm produced significant changes in the length and magnitude of cycles, providing insight into the complex system and giving scientists a new tool to further ...

Clues to aging found in stem cells' genomes

February 13, 2018
Little hints of immortality are lurking in fruit flies' stem cells.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.