Association Of Alpha-2 Macroglobulin Genetic Polymorphism With Parkinson's Disease And Essential Tremor

Background: Parkinson disease (PD) and Essential Tremor (ET) are bothdiseases of movement disorder, which are associated with disfunction of dopaminergic neurons in central neurous system. Both of their pathogenies are unknown. The present studies have suggested that they are both not only related to heterogenous factors, but also have some interrelation probably. As one of proteolytic inhibitors, a 2-macroglobulin( a 2M ) can prevent the fibril formation of (3 -amyloid peptide (Aβ ) to improve the ability to resist the toxicity of Aβ , affect the level of dopamine as well. So most researchers speculate this proteolytic inhibitor may play an important part in disfunction of dopaminergic neurons. So far the most related gene had located in its chromosome 12, a valinel000isoleucine (Val/Ile) in exon 24 and a pentanucleotide deletion/insertion ( his/Del) in the 5'splice site of exon 18. We studied polymorphism of a2M to analyze the association between the genetic susceptibility of PD or ET and healthy controls in North China .Objective: To study the relationship of genetic polymorphism of alleles a 2M24 Val/Ile and 18 Ins/Del with PD or ET patients, and research the correlation and proper mechanisms of PD and ET in North China.Methods: Using polymerase chain reaction and restrictive fragment length polymorphism (PCR-RFLP) method to investigate the distribution of genetypes and genetic alleles, a 2M 24 Val/Ile and 18 Ins/Del, in a case-control study of 872004idiopathic PD, 73 ET patients and 100 randomly selected healthy control subjects in North China.Results: (1) In the genetic analysis of cc2M 24 Val/Ile, allelic and genotypicdistribution was different significantly in PD, ET and controls(P<0.05). There was no difference between ET patients and controls in allelic and genotypic distribution(P>0.05). The allele Val and genotype Val/Ile were higher significantly in PD patients than in ET patients or controls(P<0.05). (2) In the genetic analysis of a 2M 18 Ins/Del, it showed no significant difference in allelic and genotypic distribution between PD, ET patients and selected controls(P>0.05).Conclusions: (1) There may be association of polymorphism in a 2M 24Val/Ile with genetic susceptibility of PD patients, and the allele Val and genotype Val/Ile made the occurent risk of PD rise. There may be no association between polymorphism of a 2M 24 Val/Ile and genetic susceptibility of ET patients. (2) There may be no association between polymorphism of a2M 18 Ins/Del and genetic susceptibility of PD or ET in North China.