Altered spontaneous brain activity in essential tremor with and without resting tremor: a resting-state fMRI study.

OBJECTIVES: Essential tremor with resting tremor (rET) often exhibits severer clinical features and more extensive functional impairment than essential tremor without resting tremor (ETwr). However, the pathophysiology of rET is still unclear. This study aims to use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the alterations of brain activity between the drug-naïve patients of rET and ETwr. METHODS: We recruited 19 patients with rET, 31 patients with ETwr and 25 healthy controls (HCs) to undergo a 3.0-T rs-fMRI examination. The differences of regional brain spontaneous activity between the rET, ETwr and HCs, as well as between total ET (rET + ETwr) and HCs were measured by amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The relationships between the altered brain measurements and the clinical scores were analyzed. RESULTS: Compared with HCs, both ET subgroups showed significantly decreased ALFF or fALFF values in the basal ganglia, inferior orbitofrontal gyrus and insula. The rET group specifically showed decreased ALFF values in the hippocampus and motor cortices, while the ETwr group specifically evidenced increased ALFF and fALFF values in the cerebellum. DISCUSSION: Regional spontaneous activity in rET and ETwr share common changes and have differences, which may suggest that the functional activities in the limbic system and cerebellum are different between the two subtypes. Improved insights into rET and ETwr subtypes and the different brain spontaneous activity will be valuable for improving our understanding of the pathophysiology of the disease.

Patterns of intrinsic brain activity in essential tremor with resting tremor and tremor-dominant Parkinson's disease.

The clinical pictures of essential tremor (ET) with resting tremor (rET) and tremor-dominant Parkinson's disease (tPD) are often quite mimic at the early stage, current approaches to the diagnosis and treatment therefore remain challenging. The regional homogeneity (ReHo) method under resting-state functional magnetic resonance imaging (rs-fMRI) would help exhibit the patterns in neural activity, which further contribute to differentiate these disorders and explore the relationship between symptoms and regional functional abnormalities. Sixty-eight Chinese participants were recruited, including 19 rET patients, 24 tPD patients and 25 age- and gender-matched healthy controls (HCs). All participants underwent clinical assessment and rs-fMRI with a ReHo method to investigate the alterations of neural activity, and the correlation between them. Differences were compared by two-sample t-test (corrected with AlphaSim, p < 0.05). Compared with HCs, patients' groups both displayed decreased ReHo in the default mode network (DMN), bilateral putamen and bilateral cerebellum. While tPD patients specifically exihibited decreased ReHo in the bilateral supplementary motor area (SMA) and precentral gyrus (M1). The correlation analysis revealed that ReHo in the bilateral putamen, right SMA and left cerebellum_crus I were negatively correlated with the UPDRS-III score, respectively, in tPD group. Our results indicated the rET patients may share part of the pathophysiological mechanism of tPD patients. In addition, we found disorder-specific involvement of the SMA and M1 in tPD. Such a distinction may lend itself to use as a potential biomarker for differentiating between these two diseases.

Association of three candidate genetic variants in ACMSD/TMEM163, GPNMB and BCKDK /STX1B with sporadic Parkinson's disease in Han Chinese.

Large-scale meta-analyses of genome-wide association studies have identified that polymorphisms ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 to be the risk loci for Parkinson's disease (PD) in a Caucasian population. However, the role of these three polymorphisms in a Han Chinese population from mainland China still remains to be clarified. We conducted a large sample study to examine genetic associations of rs6430538, rs199347 and rs14235 with PD in a Han Chinese population of 989 sporadic PD patients and 1058 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. In addition, we conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, no significant differences were found in genotype and allele frequency distribution between PD patients and controls for the three loci, even after being stratified by age at onset. Moreover, we demonstrated that minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our study is the first to demonstrate that ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 do not confer a significant risk for sporadic PD in mainland China. Therefore, more replication studies in additional Chinese population and other cohorts and functional studies are warranted to further clarify the role of the three loci in PD susceptibility.

The association between HSD3B7 gene variant and Parkinson's disease in ethnic Chinese.

Objectives: Studies at the genomewide level of Parkinson's disease (PD) suggested a significant association between the Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta isomerase 7 (HSD3B7) gene rs9938550 variant and a decreased risk for PD. But its effect has only been discussed in Caucasian populations, and no phenotypic characteristics were included. To investigate the novel variant for PD in Chinese Han populations, we performed an association analysis of rs9938550 variant in a large cohort. Methods: Using a case-control methodology, a total of 2,239 subjects (1,072 sporadic patients with PD and 1,167 control) were genotyped and the genetic association was analyzed. Results: No significant association was found between allele A of rs9938550 and PD in the entire cohort (p = .079). However, the frequency of allele A was lower in late-onset PD (LOPD) as compared with controls older than 50 years (OR = 0.62, 95% CI: 0.45-0.85, padjust = .002). Relatively lower Unified Parkinson's Disease Rating Scale scores were demonstrated in mid- to late-stage PD with GA + AA genotypes than GG genotype (padjust = .018), while other clinical features were similar between carriers and noncarriers. Conclusions: Our results support that the HSD3B7 rs9938550 variant, which is likely linked to bile acid biosynthesis, reduces the risk of LOPD in Chinese patients and might induce a benign clinical performance.

Genetic analysis of FGF20 in Chinese patients with Parkinson's disease.

Sequence variants in fibroblast growth factor 20 (FGF20) have been reported to be associated with Parkinson's disease (PD). We genotyped the rs591323 variant in a total of 2220 Han Chinese subjects, including 1051 patients with sporadic PD and 1169 controls, to investigate the association between rs591323 and the risk of PD. In addition, we also conducted a stratified analysis according to age at onset of PD and compared the clinical characteristics of AA + AG subjects with GG subjects. In this study, we confirmed that the A allele of rs591323 in FGF20 reduces the risk of developing sporadic PD (P = 0.013). Additionally, subjects with the AA + AG genotype have a reduced risk compared to individuals with the GG genotype (P = 0.024). This association was significant among females (P = 0.036), but was not significant among males (P = 0.266). Furthermore, no significant association was observed among either the early-onset PD group (P = 0.051) or the late-onset PD group (P = 0.187). Moreover, we demonstrated that the AA + AG subjects could not be distinguished from the GG subjects based on their clinical features. Our study is the first to demonstrate that FGF20 (rs591323) is associated with a lower risk of PD in a Southern Han Chinese population from mainland China.

Genetic association study between RIT2 and Parkinson's disease in a Han Chinese population.

Recent several meta-analyses and certain case-control studies suggested that the Ras-like without CAAX 2 (RIT2) rs12456492 increased the risk of Parkinson's disease (PD) in Asian and Caucasian populations. However, as so far, the association between RIT2 rs12456492 and PD is still controversial. We investigated genetic association of RIT2 rs12456492 with PD susceptibility in a Han Chinese population of 1747 ethnic Han Chinese subjects comprising 884 PD patients and 863 healthy controls. The minor allele frequency (MAF) of G at the RIT2 rs12456492 was not significantly different between the cases and the controls. Furthermore, no significant differences were observed in genotype distribution between PD patients and healthy controls for the RIT2 rs12456492, even after being stratified by age at onset and gender. In addition, we found that no significant differences were detected in the clinical manifestations for gender, age at onset, and onset symptoms between PD patients with AG + GG genotypes and those with AA genotypes. Our study from the mainland China demonstrates that RIT2 rs12456492 do not increase the risk of developing PD. Therefore, more replication studies in additional Chinese population and other cohorts are warranted to further clarify the role of RIT2 rs12456492 in PD susceptibility.

Genetic analysis of CHCHD2 gene in Chinese Parkinson's disease.

Recently, mutations in the coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) gene have been identified in Japanese families with autosomal dominant Parkinson's disease (PD) and two single nucleotide variants (rs10043 and Pro2Leu) increased risk of sporadic PD. The role of CHCHD2 in PD susceptibility in other Asian populations still remains to be clarified. In a large Chinese cohort from mainland China (31 familial PD patients, 1,027 sporadic PD patients, and 1,095 health controls), we examined the association of rs10043 and Pro2Leu variants in CHCHD2 with PD. All subjects were homozygous for rs10043. Moreover, we detected six patients (0.57%, one of the six patients has family history) and three controls (0.27%) with a heterozygous Pro2Leu variant. Though the frequency of Pro2Leu variant was two times higher in PD compared to controls, the difference did not reach significance in genotypic distribution (P = 0.47) or allelic distribution (P = 0.47). However, our meta-analysis in Asian populations revealed that the frequency of Pro2Leu variant was significantly higher in PD patients than in controls (P = 0.0002). Our study suggests that Pro2Leu in CHCHD2 may be a risk factor for PD among Asians. © 2016 Wiley Periodicals, Inc.

Association of three candidate genetic variants in RAB7L1/NUCKS1, MCCC1 and STK39 with sporadic Parkinson's disease in Han Chinese.

Previous studies identified that polymorphisms RAB7L1/NUCKS1 rs823118, MCCC1 rs12637471 and STK39 rs1955337 to be the risk loci for Parkinson's disease (PD) in a Caucasian population. However, the characteristics of these three polymorphisms in a Han Chinese population from mainland China were unknown. We examined genetic associations of rs823118, rs12637471 and rs1955337 with PD susceptibility in a Han Chinese population of 1016 sporadic PD patients and 1069 controls. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. In this study, the minor allele frequency (MAF) was significantly different of RAB7L1/NUCKS1 rs823118 (P = 0.003) and MCCC1 rs12637471 (P = 0.008) between cases and controls. Subjects of RAB7L1/NUCKS1 rs823118 with CC+CT genotypes had a decreased risk compared to those with TT genotype (P = 0.001) and this association also can be seen among younger population (<50 years, P = 0.011). For the MCCC1 rs12637471, subjects with GA+GG genotypes had an increased risk compared to those with AA genotype (P = 0.017). However, we did not observe any significant difference in allele and genotype distribution between PD patients and controls for rs1955337 in STK39. In addition, minor allele carriers cannot be distinguished from non-carriers based on their clinical features of the three loci. Our study provides strong support for the susceptibility role of rs823118 and rs12637471 in sporadic PD in a Han Chinese population.

[The study of esophageal cancer risk associated with polymorphisms of DNA damage repair genes XRCC4 and RAD51].

OBJECTIVE: Investigate the association between genetic polymorphism of DSBs repair gene XRCC4, RAD51 and susceptibility to esophageal cancer (EC). METHODS: A hospital based case-control study with 123 EC cases and 61 controls in a Chinese population was conducted. PCR-RFLP was applied to investigate the genotype of XRCC4 promoter G-1394T (rs6869366) and RAD51-G135C and then statistical analysis was conducted by calculating the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: A significant difference of XRCC4-1394 polymorphism was observed between EC cases and controls (P < 0.05). Carriers of the XRCC4 rs6869366 G allele (GC+GG) were at a higher risk of developing EC with the TT genotype as reference (OR = 3.022, 95% CI = 1.487-6.142, P = 0.002). When GG served as the reference group of RAD51-G135C allele, variant genotype (GC and CC) had a significant increased risk of lung cancer (OR = 3.643, 95% CI = 1.501-8. 842, P < 0.05). CONCLUSION: Our findings indicated that genetic variants in DNA repair pathways may be involved in esophageal tumorigenesis. XRCC4 G-1394T and RAD51-G135C conferred risk for the process of developing EC.