Genetic clues to IgA nephropathy

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Genetic clues to IgA nephropathy

Postby whbio » Mar 07 2017 2:55 pm

An international research team consisting of researchers from America, Germany, France, Italy, China, and Japan, now provides insights into the genetic mechanism of Berger's disease, or referred to as IgA nephropathy, which is an inflammation of the glomeruli of the kidney. The disease occurs when a type of antibody called immunoglobulin A (IgA) lodges in the kidneys, causing inflammation that hampers the normal function of the glomeruli. Berger's disease progresses over 10-20 years and may finally lead to kidney failure, which is not reversible.

The study enrolls 2,633 subjects of European and East Asian ancestry, populations that have higher incidence of the disease. The researchers performed a quantitative genome-wide association study for serum levels of galactose-deficient IgA1 in these people and observed that genetic variants in two genes, C1GALT1 and C1GALT1C1, were much more common in people with high levels of Gd-IgA1.

O-glycosylation is a fundamental post-translational modification of proteins, and abnormalities in this modification have been linked to many different diseases, including Berger's disease. Prior studies have suggested that structural abnormalities of O-glycosylation of IgA antibodies play a role in mesangial IgA deposition. Galactose-deficient IgA1 is considered a marker for Berger's disease. But the molecular basis of aberrant O-glycosylation in this disease is not fully understood.

The C1GALT1 and C1GALT1C1 genes are located on different chromosomes, but they both encode proteins essential for the proper glycosylation of IgA1. In vitro siRNA knock-down studies confirmed that both the two genes influence the rate of secretion of Gd-IgA1. Collectively, the findings provide clues to the genetic regulation of O-glycosylation.

Kidney disease usually cannot be cured. At late stage of kidney disease, some patients must go on dialysis or receive a kidney transplant. Further, Berger's disease patients have a higher recurrence rate after kidney transplant. This study could lead to a deeper understanding of Berger's disease and many other diseases associated with O-glycosylation defects. Further, larger population-based research is needed to identify additional genetic determinants of O-glycosylation defects.

This work is a collaboration of Columbia University, University of Alabama at Birmingham, Juntendo University Faculty of Medicine, University School of Medicine, Bayer Pharma AG, RWTH University of Aachen,University North Hospital, Shanghai Jiao Tong University School of Medicine, Peking University Institute of Nephrology, University of Brescia, and Le Bonheur Children's Hospital. The study is published February 10, 2017 in PLOS Genetics. Cusabio offers various antibodies including IgA and proteins including C1GALT1 and C1GALT1C1. Go to
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