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Objective: Parkinson's disease (PD) has been identified as a genetically influenced disease linked to various genetic loci. Previous studies have suggested that neurodegenerative illnesses, including PD, Alzheimer's disease, and Amyotrophic lateral sclerosis (ALS), may share certain genetic loci. Recently, the NEK1 gene was identified as overlapping between PD and ALS. We therefore wanted to explore the potential association between the NEK1 gene single nucleotide polymorphisms (SNPs) and the clinical features and pathophysiology of sporadic PD in a northern Chinese population., Methods: A total of 510 sporadic PD patients and 510 age- and sex-matched healthy controls (HCs) were included in this study. Two SNPs (rs4563461 and rs66509122) of the NEK1 gene were genotyped using polymerase chain reaction (PCR). And we analyzed the association between NEK1 gene polymorphisms and clinical manifestations., Results: Allele T (C vs. T, P = 0.018) and genotype TT (CC vs. TT: P = 0.021) of rs66509122 among PD group and HCs were significantly different. In addition, we discovered that the rs66509122 genotype TT was associated with depression in early-onset PD (EOPD) (P = 0.031) and diabetes in female PD (P = 0.032). Unfortunately, no distinct correlation of rs4563461 polymorphisms with sporadic PD susceptibility was found in either the overall group (C vs. T, P = 0.086) or other subgroups. However, the T allele of rs4563461 was significantly correlated with sleep disorders in the PD group, especially in the late-onset PD (LOPD) group and male PD group., Conclusion: This study found that the NEK1 rs66509122 polymorphism was associated with a lower risk of sporadic PD, while T allele of rs66509122 may be a protective factor for PD. The NEK1 rs4563461 and rs66509122 polymorphisms both showed correlations with some non-motor symptoms in sporadic PD patients. Further research with a larger sample and varied ethnic groups is needed to investigate the role of NEK1 gene polymorphisms in the pathophysiology of PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The synaptic vesicle glycoprotein 2 (SV2) has been implicated in synaptic function throughout the brain. Accumulating evidence investigated that SV2C contributed to dopamine release and the disrupted expression of SV2C was considered to be a unique feature of PD that may facilitate dopaminergic neuron dysfunction., Objective: This study aimed to examine the relationship between the SV2C rs1423099 single nucleotide polymorphism and sporadic Parkinson's disease (PD) in the Chinese Han population., Materials and Methods: This study enrolled 351 patients with sporadic PD and 240 normal controls in Chinese Han population. Peripheral blood DNA was extracted by DNA extraction kits and the rs1423099 genotype was analyzed by Agena MassARRAY DNA mass spectrometry. The differences in genotype and allele distribution frequencies between PD patients and control groups were compared using chi-squared tests or Fisher's exact tests., Results: No statistical difference was revealed in age and sex distribution between the cases and control groups, and the distribution of genotype and allele frequencies was consistent with the Hardy-Weinberg equilibrium test. In SV2C rs1423099 dominant model, the frequency of the CC/CT genotype was significantly higher in the PD group compared to the control group (OR = 4.065,95% CI: 2.801-10.870, p = 0.002). Nevertheless, in the recessive model, CC or CT/TT genotypes have no statistical difference in the two groups (p = 0.09). Additionally, in allelic analysis, the C allele was investigated to increase the risk of PD (OR = 1.346, 95% CI: 1.036-1.745, p = 0.026); Furthermore, subgroup analysis suggested that those carrying the C allele in the male subgroup were at a higher risk to afflicted with PD (OR = 1.637, 95% CI: 1.147-2.336, p = 0.006)., Conclusion: SV2C rs1423099 single nucleotide polymorphism was associated with sporadic Parkinson's disease in the Chinese Han population, particularly in males., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Parkinson's disease (PD) represents the multisystem illness involving immunological and neuroinflammatory dysfunction. The present work focused on evaluating link of CD33 single nucleotide polymorphisms (SNPs) with PD vulnerability of the northern Chinese Han people, considering CD33's role as a critical immunoregulatory receptor in neuroinflammatory responses., Methods: The present case-control study included 475 PD cases together with 475 normal controls. A further division of PD patients into two categories was made: 74 patients with early-onset PD (EOPD; onset age ≤ 50 years) and 401 patients with late-onset PD (LOPD; onset age > 50 years). DNA extraction was conducted, followed by genotyping for 2SNPs of CD33 polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)., Results: Alleles (G vs. A, P = 0.028) and AA genotypes (P = 0.042) of rs12985029 were significantly different between the groups. Distinctions were observed between the two groups in the recessive, co-dominant, and additive models (nominal P = 0.030, nominal P = 0.045, and P = 0.032). AA genotype frequency among male PD was higher compared to corresponding male controls (P = 0.034), and in the male group allele A was a factor causing the disease (P = 0.026). The rs12985029 genotypes and allele frequency were different in EOPD compared with LOPD (P = 0.002, P = 0.002, respectively), and in LOPD group relative to healthy control group (P = 0.020 and P = 0.004, separately). Regarding the rs3826656 polymorphism, the frequency of GA genotype was higher in the control group than in the case group (nominal P = 0.036). Overdominance and co-dominant models were different between these groups (P = 0.026, nominal P = 0.030). Subgroup analysis revealed genotype frequency differences between rs3826656 LOPD group and control group (P = 0.018). Furthermore, relationship between rs3826656 and rs12985029 (D' = 0.162, r2 = 0.021) did not reach a complete level of linkage disequilibrium (LD) of northern Chinese Han people., Conclusion: This study establishes an association between CD33 rs12985029 and rs3826656 polymorphisms and PD risk among the selected northern Chinese Han people. The GA genotype, rs3826656, may act as a protective factor against PD, while the A allele, rs12985029,could be genetic risk factor related to PD. Future research should include larger sample sizes and other human populations to further investigate how CD33 polymorphisms contribute to PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Genetic factors play an important role in early-onset Parkinson's disease (EOPD). The genetic spectrum of patients with EOPD varies widely among different ethnicities, with extensive investigations having been performed in Caucasian populations; however, research in Chinese populations remains limited. In this study, we performed multiplex ligation-dependent probe amplification assay and whole-exome sequencing in 15 unrelated Chinese EOPD patients with age of onset before 40 years. Among them, a patient carried compound heterozygous exon duplications in Parkin (exon 3 duplication and exon 4 duplication) (6.67 %) and two patients carried the homozygous pathogenic variant (p.D331Y) in PLA2G6 (13.33 %). Three novel variants in EIF4G1 (p.P1043S, p.R1505Q, and p.P266A) were identified and classified as uncertain significance. Additionally, a risk variant in GBA (p.L483P) was detected in one patient (6.67 %). PLA2G6 (13.33 %) was the most common causative gene among our EOPD patients. Furthermore, detailed clinical features were presented. Our results broaden the genetic spectrum and clinical phenotypic spectrum of EOPD patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Genetic variants of AKT1 have been shown to influence brain function of Parkinson's disease (PD) patients, and in this paper our aim is to investigate the association between the three single-nucleotide polymorphisms (rs2498799; rs2494732; rs1130214) and PD in Han Chinese. 413 Han Chinese PD patients and 450 healthy age and gender-matched controls were genotyped using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Both the patient and control groups show similar genotype frequencies at the three loci: rs2498799, rs2494732 and rs1130214. We are able to identify a significant difference in the frequencies of genotype (p=0.019) and G allele (OR=0.764, 95% CI=0.587-0.995, p=0.045) both at rs2498799 between the patient and control groups. Furthermore, the association of subjects with GG genotypes versus those with GA+AA genotype remain significant after adjusting for age in the Han Chinese female cohort (OR=0.538, 95%CI=0.345-0.841, p=0.006), which is especially evident in the late-onset cohort (OR=0.521, 95%CI=0.309-0.877, p=0.012). In contrast, allele frequencies at rs2494732 and rs1130214 were similar between patients and controls in all subgroup analyses. These results suggest that polymorphism of AKT1 locus is associated with risk of PD and that the G allele at rs2498799 may decrease the risk of PD in the North-eastern part of Han Chinese female population., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Several evidences have suggested that the brain-derived neurotrophic factor (BDNF) gene may be involved in the pathogenesis of bipolar disorder (BPD), but not all studies get the same result. The paper investigated two genetic polymorphisms of BDNF, C-270T and Val66Met, in a case-control design for their association with BPD. Sixty-seven patients of early age of onset and 130 patients of late age of onset were selected for study and 208 healthy individuals were used as controls. No significantly statistical differences of these two polymorphisms were found in genotypes or allele frequencies between either overall patients or late age of onset patients and normal control subjects. However, the frequency of the Val allele of the Val66Met polymorphism was found to have significantly increased in the subgroup patients with early age of onset as compared with the controls (genotype: chi(2)=6.602, d.f.=2, P=0.037; allele: chi(2)=6.223, d.f.=1, P=0.015). The study demonstrates that the BDNF C-270T and Val66Met polymorphisms are unlikely to contribute to the genetic predisposition to BPD as a whole. But Val66Met may be associated with susceptibility to the early age of onset subset of the disorder, further studies designed to explore the relationship in a larger population may be warranted.