Medical genetics: Gene markers of kidney disease
Published online 06 June 2012
Variations in immune genes associated with increased susceptibility to common kidney disease
IgA nephropathy (IgAN) is the most common condition affecting the glomeruli, or small blood vessels in the kidney. It is characterized primarily by the deposition of IgA antibodies in the glomeruli, which leads to inflammation and scarring of the blood vessels. The disease is more prevalent in Asian than in Western countries, and although genetic and environmental factors play a role in its development, very little is known about the genetic risk factors involved.
A large team of researchers led by Jianjun Liu at the A*STAR Genome Institute of Singapore have identified a number of genetic variants that are associated with increased risk of a common kidney disease called IgAN in Chinese individuals of Han descent1.
Liu and his co-workers performed a genome-wide association study comparing the genomic data of nearly 1,500 Han Chinese individuals with IgAN with those of approximately 2,700 healthy controls. In the first phase of the study, they analyzed almost 450,000 common single nucleotide polymorphisms (SNPs), or sequence variations at individual positions in the DNA sequence. This confirmed that a number of known genetics variants are associated with increased susceptibility to IgAN.
The researchers also identified several more previously unknown genetic variants. After confirming these initial findings, they analyzed these genetic variants in another 2,700 individuals with IgAN and about 3,500 controls.
Some of the newly identified SNPs lie within the region of the genome containing the major histocompatibility complex (MHC) genes, which encode proteins that are critical for proper function of the immune system. Other SNPs were found in the genes encoding tumour necrosis factor, a signaling molecule that is important for the development of B cells of the immune system, and α-defensins, a group of molecules that have antibiotic properties and are involved in the inflammatory response to infection. They also provide migratory cues for immune cells and induce them to release small signaling molecules called cytokines.
The findings show that variations in genes involved in immunity and inflammation can influence susceptibility to IgAN and the development of the disease.
“These novel SNPs have not been studied in non-Chinese populations yet, so we don't know whether they will show the similar association in other populations,” says Liu. “The SNPs only explain a small proportion of genetic risk for IgAN and many additional genetic risk variants need to be discovered. We are collaborating with other groups on a meta-analysis of IgAN where independent GWAS datasets will be combined to discover new variants.”
The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore
- Yu, X.-Q. et al. A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nature Genetics 44, 178–182 (2012). | article