TL;DR
Serum miR-146a demonstrated outstanding diagnostic accuracy and correlated inversely with PD severity, and was identified as an independent protective factor for PD, with the G allele exerting a protective effect.
An important role of neuroinflammation in the pathogenesis of Parkinson’s disease (PD) has been proposed. Since some microRNAs (miRNAs), and miR-155 in particular, are involved in neuroinflammatory processes, a previous study reported an association between one of the most common single nucleotide variants (SNVs), rs767649, in the MIR155 gene, and risk for PD. The aim of the current study was to replicate this finding in a larger Spanish population case–control series. We analyzed genotype and allele frequencies of the MIR155 rs767649 SNV in a Spanish Caucasian cohort consisting of 459 PD patients and 460 age- and sex-matched healthy controls, using a TaqMan allelic discrimination assay specifically designed for rs767649. The genotype frequencies of the MIR155 rs767649, under codominant, dominant, recessive, and overdominant inheritance models, as well as allelic frequencies, showed no significant differences between PD patients and healthy controls. Likewise, the age at PD onset did not differ among the three MIR-155 rs767649 genotypes. These data did not identify a statistically significant association between MIR155 rs767649 variants and PD risk. However, the low frequency of the variant allele resulted in limited statistical power, and modest genetic effects cannot be excluded.
Abstract Aim To evaluate six VEGFA polymorphisms (rs1570360, rs699947, rs3025033, rs2146323, rs1413711 and rs833061) and serum VEGFA concentrations in 270 Lithuanian patients with multiple sclerosis (MS) and 270 matched healthy controls. Methods Genotyping was performed using real-time PCR, and serum VEGFA levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were conducted using IBM SPSS version 31.0. Results Nominal differences in VEGFA genotype and allele distributions were observed in sex- and age-stratified analyses. Among females, the rs1413711 C allele was more frequent (p = 0.005), whereas the rs833061 C allele was less frequent (p = 0.006), in MS patients than controls. In participants aged >38 years, the rs1413711 C allele was also more frequent in MS cases (57.5% vs. 46.0%, p = 0.008). Logistic regression identified nominal associations, particularly for rs1413711, rs699947 and rs833061, but none remained significant after correction for multiple testing. Serum VEGFA levels were higher in MS patients than controls (p = 0.004). Nominal genotype-related differences in serum VEGFA levels and haplotype associations with reduced MS odds were also observed, but did not remain significant after multiple-testing correction. No consistent associations were found between VEGFA variants and clinical parameters. Conclusion VEGFA genetic variation and elevated serum VEGFA may be associated with MS, but the genetic findings require confirmation in larger independent cohorts.
Background Transmembrane protein 106B (TMEM106B) variations not only act as genetic modifiers of the risk of developing frontotemporal lobar degeneration but also correlate with the heterogeneity of clinicopathological phenotypes in other neurodegenerative diseases. However, the roles of TMEM106B in Parkinson’s disease (PD) are sparsely explored. This study aims to explore whether TMEM106B variants influence the trajectories of clinical phenotypes in PD. Methods We longitudinally followed 241 PD patients and genotyped their single nucleotide polymorphism (SNP) of rs3173615. Patients were categorized according to rs3173615 genotypes into GG (major allele homozygotes), GC (heterozygotes), and CC (minor allele homozygotes) groups. All patients completed clinical evaluations and neuropsychological tests at baseline and every follow-up. Linear mixed-effects models were adopted to evaluate the association between rs3173615 genotypes and longitudinal disease progression in PD. Results At baseline, both the GG and GC groups presented less severe excessive daytime sleepiness than the CC group, and no association between the remaining clinical characteristics and the genotypes of rs3173615 was observed among the three groups. Longitudinally, compared with the CC group, the GC group manifested a significantly faster exacerbation of depression, visuospatial function and quality of life (QoL), and the GG group showed the same tendency as the GC group, though without statistical significance. Conclusion TMEM106B rs3173615 is a genetic modifier for the trajectory of depression, visuospatial function and QoL in PD. Our findings suggest the potential involvement of TMEM106B in the pathogenesis of disease progression in PD, especially in the deterioration of depression, cognition and QoL.
Objectives: To determine the association of polymorphism rs10741657 in the CYP2R1 gene with vitamin D deficiency in apparently healthy subjects. Method: The prospective, case-control study was conducted from June 2023 to January 2024 at the CREAM Lab of Army Medical College, Rawalpindi, and comprised vitamin D-deficient cases in group A and healthy controls in group B. Genotyping of rs10741657 polymorphism in the CYP2R1 gene was performed using allele-specific polymerase chain reaction (AS-PCR). Genotypic and allelic frequencies, Hardy–Weinberg equilibrium, and genetic inheritance models were analysed using SNPStats, a web-based statistical software for genetic association studies. Results: Of the 300 subjects with a mean age of 43.56 ± 15.26 years, 150 (50%) were in group A, comprising 91 (61%) females and 59 (39%) males, with a mean age of 44.49 ± 15.12 years. There were 150 (50%) controls in group B, including 83 (55%) males and 67 (45%) females, with a mean age of 42.63 ± 15.40 years. The genotypic frequencies in group A were A/A 45(30%), A/C 101(67.34%), C/C 4(2.66%). The corresponding values in group B were 39(26%), 110(73.34%) and 1(0.66%). The allele frequency of A was 191 (64%) in vitamin D-deficient cases and 188 (63%) in healthy controls (p = 0.8775), while the C allele frequency was 109 (36%) in cases and 112 (37%) in controls (p = 0.8401). The genotype frequencies in cases were A/A 45 (30%), A/C 101 (67%), and C/C 4 (2.67%), compared to A/A 39 (26%), A/C 110 (73%), and C/C 1 (0.67%) in controls, with no statistically significant difference observed between the groups (p > 0.05). The inheritance genetic models suggested no association with vitamin D deficiency (p>0.05); codominant model – A/C odds ratio 0.70 (95% confidence interval: 0.45-1.23), C/C odds ratio 4.00 (95% confidence interval: 0.45-36.96); dominant model odds ratio 0.80 (95% confidence interval: 0.49-1.35); recessive model odds ratio 4.00 (95% confidence interval: 0.45-36.96); and overdominant model odds ratio 0.70 (95% confidence interval: 0.45-1.23). Conclusion: The A allele was found to be the most common variant of rs10741657 in both the groups. The rs10741657 polymorphism was not a risk for the susceptibility to vitamin D deficiency. No correlation of genotype with serum vitamin D levels was noted. Key Words: Allele-specific polymerase chain reaction, Single nucleotide polymorphism, Calcitriol, 25 Hydroxylase, Vitamin D binding protein.