HLA region associated with Parkinson's disease

18 August 2010

Parkinson’s disease is a common neurological condition that affects motor and cognitive disability with symptoms getting worse over time. According to Parkinson’s support and research charity Parkinson’s UK, around one in every 500 people has Parkinson’s, meaning around 120,000 cases in the UK alone. Over the past few years, several genome-wide association studies (GWAS) have been conducted but these studies have only really replicated known associations with the SNCA and MAPT genes with other genes slowly starting to be implicated (see previous news). A study recently published online in the journal Nature Genetics has replicated these known associations and also identified a new interesting association with the HLA region.

The study by Hamza et al. reports a GWAS involving 2,000 Parkinson’s patients and 2,000 controls of European descent with information at over 800,000 SNPs [Hamza et al. (2010) Nat Genet 15 August doi:10.1038/ng.642]. This work confirmed the known susceptibility regions at SNCA and MAPT and also uncovered a novel association located within the MHC/HLA, a region known to harbour genes involved in the immune system. Both the SNCA rs356220 SNP and the HLA-DRA rs3129882 SNP reached genome-wide significance. This HLA SNP also replicated in two independent datasets with overall associations slightly stronger in sporadic Parkinson’s patients as well as those with late-onset Parkinson’s. A previously suggested association with the GAK gene was also replicated through additional analyses. Although the researchers note that these four Parkinson’s susceptibility loci each have modest individual effects on Parkinson’s disease risk, they suggest that their cumulative effect may be quite substantial, with risk increasing up to five-fold for those individuals that carry six or more of the eight risk alleles at these four loci.
Comment: This well-conducted GWAS study identified a novel, biologically plausible candidate region involved in immunity as well as confirming previously known or suspected loci. The authors state that these results “lend strong and independent support to the involvement of neuroinflammation and humoral immunity in Parkinson’s disease pathogenesis”. There is currently no cure for Parkinson’s and so it is hoped that these insights will lead to treatments but as Parkinson’s doesn’t directly cause people to die, the development of any novel drugs to target the possible immune role in Parkinson’s may be slow.

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