Association between VPS13C rs2414739 polymorphism and Parkinson's disease risk: A meta-analysis.

OBJECTIVE: We aimed to estimate the role of vacuolar protein sorting 13C (VPS13C) gene single nucleotide polymorphism (SNP) rs2414739 variant in the risk of PD by meta-analysis. METHODS: Five eligible case-control studies including 2796 PD cases and 4138 health controls involved in this meta-analysis. The fixed or random effect model was selected based on the heterogeneity of the included studies which detected by I2 and Q tests. The association between rs2414739 polymorphism and the risk of PD was evaluated using the pooled odds ratios (OR) and 95 % confidence interval (95 %CI). Sensitivity analysis was used to test the stability of the results. Funnel plot and Begg's test were employed to verified publication bias. RESULTS: The results of our meta-analysis showed a significant correlation between VPS13C rs2424739 gene polymorphism and PD susceptibility in Allele model (A versus vs. G: OR = 1.14, 95 %CI = 1.05-1.23, p = 0.002), dominant model (GG + AG vs. AA: OR = 0.86, 95 %CI = 0.78-0.95, p = 0.004), heterozygote model (AG vs. AA: OR = 0.87, 95 %CI = 0.77-0.99, p = 0.04), homozygote model (GG vs. AA: OR = 0.76, 95 %CI = 0.60-0.96, p = 0.02). Surprisingly, we did not find a significant statistical difference between VPS13C rs2414739 polymorphism and PD risk in Chinese cohort in the regional stratified analysis. CONCLUSIONS: This meta-analysis suggests that VPS13C rs2414739 polymorphism might act as a genetic predisposition factor for PD, whereas does not include Chinese population.

CUB and Sushi Multiple Domains (CSMD1) Gene Polymorphisms and Susceptibilities to Idiopathic Parkinson's Disease in Northern Chinese Han Population: A Case-Control Study.

Evidence has shown that the CUB and Sushi Multiple Domains (CSMD1) gene is an inhibitor of the complement activation pathway and is also involved in central nervous system inflammation. Previous studies have revealed that the CSMD1 gene is related to familial Parkinson's disease. This study aimed to investigate the relationship between CSMD1 gene and susceptibility to Parkinson's disease in population of northern China. A case-control study was performed on 423 Parkinson's disease patients and 465 healthy controls matched for age and sex. DNA from enrolled subjects were extracted from the peripheral blood, and single nucleotide polymorphisms (SNPs) rs12681349 (C＞T), rs10503253 (C＞A), and rs1983474 (T＞G) within CSMD1 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequency of rs10503253 (CA versus CC : OR = 1.554, 95% CI = 1.169-2.066, p=0.002) and rs1983474 (GG versus TT : OR = 0.599, 95% CI = 0.401-0.895, p=0.012) was significantly different between PD cases and controls, but not for rs12681349. Comprehensive and subgroup analysis indicated that rs10503252 showed significant statistical differences in the dominant model (AA + CA versus CC : OR = 0.677, 95% CI = 0.517-0.886, p=0.004), late-onset cohort (CA versus CC : OR = 1.570, 95% CI = 1.159-2.126, p=0.004), and the female cohort (CA versus CC : OR = 0.687, 95% CI = 0.497-0.952, p=0.023), compared with the matched control group. The difference of recessive model of rs1983474 (GG versus TT + TG : OR = 1.837, 95% CI = 1.287-2.620, p=0.001) was significant in Parkinson's disease. According to the subgroup analysis, results indicated that late-onset cohort (GG versus TT : OR = 0.643, 95% CI = 0.420-0.985, p=0.042), male cohort (TG versus TT : OR = 2.160, 95% CI = 1.162-4.016, p=0.015), and female group (GG versus TT : OR = 0.418, 95% CI = 0.234-0.746, p=0.003) of rs1983474 were significantly associated with Parkinson's disease susceptibility. In both genotype and subgroup analysis, we failed to find any relationship between rs12681349 polymorphism and Parkinson's disease risk. Our results indicate that the rs10503253 and rs1983474 gene polymorphism may be associated with idiopathic Parkinson's disease susceptibility in Chinese population. Nevertheless, these conclusions need to be further verified by more studies.

Association between epidermal growth factor receptor gene polymorphisms and susceptibility to Parkinson's disease.

OBJECTIVE: The progressive loss of dopaminergic neurons in the mesencephalic substantia nigra is recognized as an important pathological feature of Parkinson's disease (PD). Several research studies have suggested that the EGFR signaling pathway may play a significant role in the survival and functional development of dopaminergic neurons. Therefore, genetic variations in these pathways may be related with PD susceptibility. The aim of our study was to explore the association between selected single nucleotide polymorphisms (SNPs) of the epidermal growth factor receptor (EGFR) gene, including rs730437, rs3752651 and rs11506105, and susceptibility to Parkinson's disease in a Han Chinese population. METHODS: A total of 870 Han Chinese subjects, including 435 PD patients and 435 healthy controls, were enrolled in this case-control study. Peripheral blood was obtained from all subjects for DNA extraction, and selected SNPs (rs730437, rs3752651, rs11506105) of the EGFR gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Differences in the frequencies of genotype and allele gene polymorphisms between patients with PD and healthy controls were analyzed using the Chi-square test. Logistic regression analysis was applied for calculating the odds ratios (ORs) and 95 % confidence intervals (CIs) to evaluate potential associations. RESULTS: We observed statistically significant differences in rs730437 in the additive models (AC vs. AA: P = 0.047), dominant models (CC + AC vs. AA: P = 0.024) and alleles (C vs. A: P = 0.018). Further subgroup analyses indicated that the C allele of rs730437 showed lower prevalence in the EOPD, compared with matched controls (P = 0.005). The frequency of the GG genotype and G allele for rs11506105 was lower in PD subjects than in healthy controls in the entire study population (P = 0.028, P = 0.034, respectively) and female group (P = 0.024, P = 0.007, respectively). No significant association was found between rs3752651 polymorphism and PD susceptibility in either the whole or subgroup analyses. The analysis of gene haplotypes revealed that the AAT haplotype was related with PD susceptibility. CONCLUSION: The rs730437 and rs11506105 polymorphisms, but not the rs3752651 polymorphism, of the EGFR gene may be related with susceptibility to PD in a Han Chinese population. An investigation using a larger sample size is warranted to further analyze potential associations between the EGFR gene and PD.

Association of IL-16 gene polymorphisms with sporadic Parkinson's disease in a Han Chinese population.

This study was performed to investigate the genetic association of single-nucleotide polymorphisms (SNPs) in the interleukin-16 (IL-16) gene with the risk of Parkinson's disease (PD) in a Chinese Han population. Genotyping for the rs11556218 T/G, rs1131445 T/C and rs4072111 C/T polymorphisms of IL-16 was performed using the PCR-RFLP method in 405 patients with PD and 405 healthy matched individuals. Statistically significant difference for rs4072111 could be observed in both additive model (TC vs. CC: OR=0.622, 95 % CI: 0.443-0.873, P = 0.006) and dominant model (TC+TT vs. CC: OR =0.644, 95 % CI: 0.464-0.893, P = 0.008). The frequency of the rs4072111 T allele was significantly lower in the PD patients (OR= 0.692, 95 % CI: 0.515-0.929, P = 0.014) than in the controls. In subgroup analysis, a significant difference in genotype frequency distribution (P =0.004) and allele frequency (P =0.001) was found for rs4072111 between the male PD group and the control group, similar to the findings for the late-onset Parkinson's disease (LOPD) group and the control group (P = 0.044, 0.038, respectively). Conversely, there was no significant difference in the frequencies of rs11556218 and rs1131445 between the PD patients and controls. Moreover, seven common haplotypes were detected, and the CGT and CTC haplotypes were associated with PD susceptibility in our study. Our results indicate that the IL-16 gene rs4072111 polymorphism is significantly associated with PD susceptibility in the Chinese Han population but that the polymorphisms rs11556218 and rs4778889 are not.

Association between serum bilirubin concentration and Parkinson's disease: a meta-analysis.

BACKGROUND: The antioxidant effects of bilirubin in Parkinson's disease (PD) have recently gained much attention from the research community. However, results from these studies have been conflicting. This meta-analysis is conducted to assess the relationship between the serum bilirubin concentration and the risk of PD. METHODS: Two reviewers performed a systematic literature search across five databases (MEDLINE, PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials). The case-control studies regarding bilirubin levels in PD patients published up to April 2020 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the standard mean difference (SMD) and the 95% confidence interval (CI), which were analyzed using the Stata V.12.0 statistical software. RESULTS: A total of eight studies which included 1463 PD cases and 1490 controls were incorporated into our meta-analysis. SMD analysis showed that there was a higher total bilirubin (TBIL) and direct bilirubin (DBIL) levels in PD patients compared with controls (for TBIL, SMD: 0.300, 95% CI: 0.050-0.549, P = 0.018; for DBIL, SMD: 0.395, 95% CI: 0.102-0.688, P = 0.008). However, no significant relationship was found between the serum indirect bilirubin and PD patients (SMD: -0.223, 95% CI: -0.952-0.505, P = 0.548). A subgroup analysis based on ethnicity indicated that the serum TBIL was higher in PD patients of Caucasian descent in contrast to matched healthy controls (SMD: 0.511, 95% CI: 0.324-0.698, P = 0.000, I2 = 58.0%). CONCLUSION: Higher serum bilirubin levels in PD patients suggest that bilirubin might play a role in the pathogenesis of PD and have the potential to be utilized as a biochemical marker for PD diagnosis and treatment.