The Thr105Ile Variant (rs11558538) of the Histamine N-methyltransferase Gene may be associated with Reduced Risk of Parkinson Disease: A Meta-analysis.

Background: Previous studies have reported conflicting results regarding the potential association between the risk of Parkinson's disease (PD) and the single nucleotide polymorphism, rs11558538 (Thr105Ile), in the histamine N-methyltransferase (HNMT) gene. We performed a systematic review and meta-analysis to improve our understanding of the association between them. Methods: We systematically searched several online databases to identify relevant studies regarding the association between rs11558538 and PD. We extracted data on the frequencies of genotypes (Thr/Thr, Thr/Ile, and Ile/Ile) and alleles (Thr and Ile) at the rs11558538 locus in patients with PD and healthy controls. Associations between genotype and PD risk were assessed in terms of odds ratios (OR) and 95% confidence intervals (CI). Results: The final meta-analysis included six case-control studies and data from the International Parkinson's Disease Genomics Consortium (IPDGC) data base on the association between HNMT rs11558538 and PD, involving 22,855 patients and 65,367 controls. Among the studies, substantial heterogeneity was observed (I2 = 84.42 for genotype and I2 = 73.39 for allele). Both the Ile (log OR: -0.31; 95% CI: -0.5 to -0.12; p < 0.001) and Thr/Ile+Ile genotypes (log OR: -0.32; 95% CI: -0.55 to -0.08; p < 0.001) were associated with a decreased risk of sporadic PD across all study populations. Subgroup analysis showed the protective effect of Thr/Ile+Ile genotypes in non-Chinese cohorts (log OR: -0.66; 95% CI: -0.67 to -0.04; p < 0.001) but not in Chinese cohorts (log OR: -0.26; 95% CI: -0.63 to 0.11; p = 0.13). Conclusion: Our findings suggest that the HNMT rs11558538T polymorphism may protect against PD, particularly in patients from the United States and Europe.

Meta-analysis of the association between CHCHD10 Pro34Ser variant and the risk of amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS), one of the motor neuron diseases, appears to be caused by genetic and environmental risk factors. However, the influence of Pro34Ser variant of CHCHD10 gene in increasing risk of ALS remains indeterminate. This study conducted a meta-analysis to establish the association between Pro34Ser variant of CHCHD10 gene and risk of ALS. METHODS: PubMed, Web of Science, and Embase databases were systematically searched for genome-wide association studies or case-control studies published up to March 28, 2020, on the association between Pro34Ser variant and risk of ALS. Data from eligible studies were extracted and analyzed. RESULTS: Twelve case-control studies involving 7442 patients with sporadic ALS and 75,371 controls were analyzed. The Pro34Ser variant was not associated with increased risk of ALS disease based on fixed-effects meta-analysis (Pro34Ser-positive vs Pro34Ser-negative: OR 1.23, 95% CI 0.90 to 1.69, P = 0.201). CONCLUSION: Existing evidence suggests that Pro34Ser variant in CHCHD10 is not associated with risk of ALS, particularly in Caucasian participants. However, our results ought to be validated using large, well-designed studies, especially in Asian and African populations.

Resting state fMRI reveals the altered synchronization of BOLD signals in essential tremor.

Essential tremor (ET) is one of the most common movement disorders in humans. Nevertheless, there remain several controversies surrounding ET, such as whether it is a disorder of abnormal neuronal oscillations within the tremor network. In this work, the resting-state fMRI data were collected from 17 ET patients and 17 age- and gender-matched healthy controls. First, using FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) the abnormal synchronization of fMRI signals in ET patients were investigated. Then, global functional connectivity intensity (gFCI) and density (gFCD) were analyzed in the regions exhibiting significant FOCA differences. Compared with healthy controls, patients with ET showed the increased FOCA values found in the bilateral cuneus, the left lingual gyrus, the left paracentral lobule, the right middle temporal gyrus, the bilateral precentral gyrus, the right postcentral gyrus, the pallidum and putamen. Decreased FOCA values in ET patients were located in the frontal gyrus, the bilateral anterior cingulate and the medial dorsal nucleus of right thalamus. In ET patients, significant changes in gFCI and gFCD were located in the cuneus, the middle temporal gyrus and the middle frontal gyrus. Changes in gFCI were also found in the medial frontal gyrus and thalamus in addition to changes in gFCD in the precentral gyrus. Our results provided further evidence that ET might present with abnormal spontaneous activity in the tremor network, including motor-related cotex, basal ganglia and thalamus, as well as distributed non-motor areas. This work also demonstrated that FOCA and functional connectivity have the potential to provide important insight into the pathophysiological mechanism of ET.

Altered Structural and Functional Connectivity of Juvenile Myoclonic Epilepsy: An fMRI Study.

The aim of this study was to investigate the structural and functional connectivity (FC) of juvenile myoclonic epilepsy (JME) using resting state functional magnetic resonance imaging (rs-fMRI). High-resolution T1-weighted magnetic resonance imaging (MRI) and rs-fMRI data were collected in 25 patients with JME and in 24 control subjects. A FC analysis was subsequently performed, with seeding at the regions that demonstrated between-group differences in gray matter volume (GMV). Then, the observed structural and FCs were associated with the clinical manifestations. The decreased GMV regions were found in the bilateral anterior cerebellum, the right orbital superior frontal gyrus, the left middle temporal gyrus, the left putamen, the right hippocampus, the bilateral caudate, and the right thalamus. The changed FCs were mainly observed in the motor-related areas and the cognitive-related areas. The significant findings of this study revealed an important role for the cerebellum in motor control and cognitive regulation in JME patients, which also have an effect on the activity of the occipital lobe. In addition, the changed FCs were related to the clinical features of JME patients. The current observations may contribute to the understanding of the pathogenesis of JME.

Altered Local Spontaneous Brain Activity in Juvenile Myoclonic Epilepsy: A Preliminary Resting-State fMRI Study.

Purpose. The purpose of this study was to evaluate the regional synchronization of brain in patients with juvenile myoclonic epilepsy (JME). Methods. Resting-state fMRI data were acquired from twenty-one patients with JME and twenty-two healthy subjects. Regional homogeneity (ReHo) was used to analyze the spontaneous activity in whole brain. Two-sample t-test was performed to detect the ReHo difference between two groups. Correlations between the ReHo values and features of seizures were calculated further. Key Findings. Compared with healthy controls, patients showed significantly increased ReHo in bilateral thalami and motor-related cortex regions and a substantial reduction of ReHo in cerebellum and occipitoparietal lobe. In addition, greater ReHo value in the left paracentral lobule was linked to the older age of onset in patients. Significance. These findings implicated the abnormality of thalamomotor cortical network in JME which were associated with the genesis and propagation of epileptiform activity. Moreover, our study supported that the local brain spontaneous activity is a potential tool to investigate the epileptic activity and provided important insights into understanding the pathophysiological mechanisms of JME.