Evaluation of the relationship between SORL1 gene polymorphism and Parkinson's disease in the Chinese population.

OBJECTIVE: There is increasing evidence that lysosomal pathway dysfunction is closely linked to the pathogenesis of Parkinson's disease (PD). Considering the relationship between sortilin-related receptor 1 (SORL1) and lysosomal dysfunction, the abnormal aggregation of misfolded proteins in neurodegenerative disorders, especially in PD, and that glial cell-derived neurotrophic factor (GDNF) is the most effective neurotrophic factor affecting the activity of the dopamine system, and that SORL1 may induce PD by affecting GDNF, we investigated the correlation between three genetic variants (rs1010159, rs1629493, and rs2298813) of SORL1 gene polymorphisms and the risk of PD in the northern Chinese population in order to broaden the perspective for PD therapy. METHODS: Three single-nucleotide polymorphisms (SNPs) of SORL1 genes (rs1010159, rs1629493, and rs2298813) were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) on the DNA of 400 patients with PD and 400 healthy controls matched by age and gender. The chi-square test was used to analyze the statistical differences in genotypic and allelic polymorphism frequency between PD patients and healthy controls. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate potential correlations. RESULTS: The frequencies of the T allele of rs1010159 and the A allele of rs2298813 in patients with PD were much higher than those in the controls (P = 0.003, P = 0.042, respectively). For rs1010159, subgroup analysis showed statistical changes in the frequency of the T allele in all subgroups (P = 0.021, P = 0.036, P = 0.001, P = 0.030, respectively); however, genotypic frequency distributions were statistically significant only between male patients with PD and matched healthy male controls (P = 0.001), and between early onset PD (EOPD) and late-onset PD (LOPD) and controls (P = 0.001, P = 0.001). For rs2298813, the explicit model showed that the GA + AA genotype had an increased risk of PD compared with the GG genotype (P = 0.020, OR = 1.518, 95% CI = 1.065-2.162), and the additive model showed that GA was also associated with a higher trend in PD compared with the GG genotype (P = 0.037, OR = 1.475, 95% CI = 1.024-2.125), and the allelic and genotypic frequencies of the LOPD were statistically different from those of the healthy group (P = 0.013, P = 0.044; respectively). No distinct correlation was found between rs1629493 and PD risk. The GAT haplotype, together with the AGT haplotype, was associated with PD susceptibility. CONCLUSIONS: The rs1010159 and rs2298813 polymorphisms of the SORL1 gene rather than the rs1629493 polymorphism may be implicated in the susceptibility to PD in the northern Chinese population. Studies in different ethnicities and larger populations are indispensable for understanding the intrinsic correlation between the SORL1 gene and PD pathogenesis.

Association of PGLYRP2 gene polymorphism and sporadic Parkinson's disease in northern Chinese Han population.

Gut inflammation is increasingly corroborated to take part in the pathogenesis of Parkinson's disease (PD). The PGLYRP2 gene has been proven to increase susceptibility to inflammatory bowel disease (IBD). The present study aimed to explore the genetic relationship between single nucleotide polymorphism (SNP) of the PGLYRP2 gene and the risk of sporadic PD in the Han population of northern China. The genotypes of the rs3813135 T/C, rs733731 C/T and rs892145 A/T polymorphisms of the PGLYRP2 gene in 400 Chinese Han patients with PD and 400 healthy age-and sex-matched individuals were identified by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) method. The results showed that the frequency of the rs892145 AT heterozygote significantly differed between the PD and control groups (OR = 1.459, 95%CI = 1.459-1.039, P = 0.029), as well as the early-onset PD and control groups (P = 0.024). The rs3813135 polymorphism yielded only one significant result: C allele was more common in the male PD group than in the male control group (P = 0.045). Conversely, no significant difference in the genotype frequency of rs733731 was found between the PD and control groups. Five common haplotypes were assessed, of which the TTA and TCA haplotypes were related to PD susceptibility. In summary, our results indicated that the PGLYRP2 gene is associated with sporadic PD in the Chinese Han population, in which the rs892145 AT heterozygote might increase the risk of PD and possibly the risk of early-onset PD. Moreover, linkage disequilibrium (LD) analysis showed these three PGLYRP2 polymorphisms has a strong linkage in causing mutations.