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 characterised 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
analysed 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 analysed 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 signalling 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 signalling 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 population 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
References
- 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
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