Progress and Prospects in Parkinson's Research/Causes/Inheritance/HLA
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The HLA region has been implicated in the onset of some types of familial Parkinson’s Disease.
The human leukocyte antigen (HLA) system is the name of a super locus contains a large number of genes related to immune system functions. Different classes have different functions: Its purpose came to light when the reasons for the rejections of organ transplants were evaluated.
It is found on chromosome 6.
In 2010 Hamza et al  published the results of a new human Genome-Wide Wide Association Study (GWAS). The genes of a cohort of 2,000 PD patients of Caucasian ethnicity were compared with a matched cohort of 1,986 people without the disease and significant differences were recorded.
The study confirmed previous findings of a link between the incidence of PD and variations in the SNCA, MAPT and GAK genes. It also noted a previously unrecorded PD risk for variations in the HLA genetic region, which was significant, both because it involved the human immune system, and also pointed to genetic influences in the late onset of sporadic cases of the disease.
The weight to be attached to GWAS results depends upon a number of factors:-
•The size, degree of matching and composition of the cohorts;
•Whether the findings are corroborated by repeat studies;
•The significance of the related genes.
Significant genetic variations can form a target for future therapeutic intervention but to define ”significance” it is first necessary to disentangle the process of tagging, whereby one expressed gene tags another for subsequent expression. Tagging can be multi-level and have a cascade effect within a cell, whereby one risk gene may be the progenitor of several others. Variations are also often found in intergenic (so-called ‘junk’) DNA, which regulate or mediate the expression of coding genes.
A follow-up study by Hill-Burns et al  has sought to evaluate the 107 variants located to date in the HLA region. The researchers employed a process called “step-wise conditional analysis”, which eliminated subordinate SNPs. This reduced the number of risk SNPs from 107 to 4 standalone examples, which could be the subject of further research. The implication that PD might be the result of an immunity deficiency has yet to be evaluated fully.
Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease HLA.
This will list the latest papers on this topic. You are invited to update this page to reflect such recent results, pointing out their significance.
- Hamza, T.H.; Zabatian, C.P.; Tenesa, C.P.; Laederach, A.; Montimurro, J.; Yerout, D.; .Kay, D.M.; Doheny, K.F.; Paschall ,J.; Pugh, E.; Kusel, V,I,; Collura, R.; Roberts, J, Griffith, A.; Samii, A.; Scott, W.K.; Factor, S.A.; Nutt, J. and Payami. H.(2010) Nat. Genet. 42 (9) 781-786. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.
- Hill-Burns, Erin M.; Factor, Stewart A.; Zabetian, Cyrus P.; Thomson, Glenys and and Payami, Haydeh (2011) PLoS One 6 (11). Evidence for More than One Parkinson’s Disease-Associated Variant within the Hla Region.