Abstrakt

Association of functional RAGE gene polymorphisms with Parkinson's disease in a Turkish cohort

Oguz Cilingir, Serhat Ozkan, Beyhan Durak Aras, Ebru Erzurumluoglu, Ozden Kutlay, Mehdi Akinci, Busra Emir, Aysan Afagh, Sevilhan Artan

Background: There is an increasing deal about the role of inflammation in Parkinson’s disease (PD) pathogenesis after the observation of clear evidence of immune responses close to the basal ganglia of PD patients. Although receptor of advanced glycation end-products (RAGE) has been implicated in several studies as an inflammation marker in PD; RAGE gene polymorphisms is infrequently examined. Thirty single-nucleotide polymorphisms (SNPs) including G82S (rs2070600) located in 3rd exon, -374T/A (rs1800624), -429T/C (rs1800625) and 63bp ins/del in the promoter region of the gene which may have marked effects on the expression or function of RAGE have been described to date.

Objective: To evaluate the association of RAGE gene polymorphisms with PD in a Turkish cohort.

Methods: Totally, 174 PD patients and 150 healthy-individuals were included into the study. Genotype analyses were performed using PCR-RFLP and ARMS methods.

Results: 429T>C, 374T>A, and 82G>S polymorphisms showed significant differences between PD patients and controls (p<0.001, p<0.05, p<0.001, respectively). For 82G>S polymorphism, the patients carrying mutant S allele in homozygous (p<0.00, OR=16.094) or heterozygous (p<0.00, OR=22.379) states have the highest risk for PD development.

Conclusion: The RAGE gene polymorphisms that are involved in gene expression may be associated with the susceptibility of PD and homozygous/heterozygous mutant S genotypes for the exonic 82G>S polymorphism may be an informative risk factor for PD. However, larger and different ethnical cohorts are needed to validate the results for different populations.