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

Abstract

ObjectiveThere 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. MethodsThree 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. ResultsThe 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. ConclusionsThe 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.