Genetic Clues May Help Prevent IgA Nephropathy

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Researchers have found five regions in the human genome that increase susceptibility to immunoglobulin A (IgA) nephropathy, a major cause of kidney failure worldwide. 

Some genes implicated in the study are interesting because they play a role in other immune disorders. For example, the complement factor H region, called the locus, has been associated with macular degeneration and susceptibility to meningococcal infection.

The genes identified in the Asian population were also found in North American and Mediterranean populations, suggesting that the genetic basis for the disease is similar in these populations.

“The cause and development of IgA nephropathy is poorly understood. Many biological pathways have been suggested, but none has been conclusive until now,” said principal study investigator Ali Gharavi, MD of the Division of Nephrology at Columbia University in New York. “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.”

Study findings appear in Nature Genetics (2011;43:321-327). The ongoing genome-wide association study so far has looked at the genes of 3,144 people of Chinese and European ancestry, all of whom have IgA nephropathy. 

IgA nephropathy appears to be a benign condition in some people, causing only occasional hematuria, while others progress to end-stage renal disease.

The study may be able to address why some patients with IgA nephropathy end up on transplant waiting lists. The worldwide prevalence of IgA nephropathy appears to be highest in Asia and southern Europe, and is responsible for most cases of kidney failure in those populations. The U.S. prevalence is much lower (approximately 10%), although Native Americans from New Mexico have reported rates as high as 38%.

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