Association of COMT rs4680 and MAO-B rs1799836 polymorphisms with levodopa-induced dyskinesia in Parkinson's disease-a meta-analysis.

BACKGROUND AND PURPOSE: Polymorphisms of the catechol-O-methyl transferase (COMT) or monoamine oxidase B (MAO-B) genes may affect the occurrence of dyskinesia in Parkinson's disease (PD) patients. However, the findings are inconsistent. Thus, we performed a meta-analysis to assess whether COMT and MAO-B genetic variants are associated with an increased incidence of levodopa-induced dyskinesia (LID) in PD patients. METHODS: A literature search of PubMed, Embase, and Cochrane Library was conducted to identify relevant studies published up to January 2021. The strength of the association between the polymorphisms and LID susceptibility was estimated by odds ratio (OR) and associated 95% confidence interval (CI). The pooled ORs were assessed in different genetic models. RESULTS: Ten studies involving 2385 PD patients were included in the meta-analysis. Analysis of pooled ORs and 95% CIs suggested that the AA genotype of COMT(rs4680) was associated with LID (OR = 1.39, 95%CI: 1.02-1.89, P = 0.039) in the recessive model, and this correlation was more obvious in Brazilian samples in the analysis stratified by ethnicity. For the AG genotype of MAO-B(rs1799836), the pooled OR was 1.66 (95% CI: 1.04-2.65, P = 0.03) in patients with LID versus those without LID in the heterozygote model. CONCLUSIONS: Our meta-analysis implicates the AA genotype of the COMT rs4680 polymorphism as potentially increasing the risk of LID in a recessive genetic model for PD patients. Furthermore, the AG genotype of the MAO-B rs1799836 polymorphism may influence the prevalence of LID in PD patients in the heterozygote model. However, further well-designed studies with larger PD patient cohorts are required to validate these results after adjusting for confounding factors.

Moderate hypothermia induces protection against hypoxia/reoxygenation injury by enhancing SUMOylation in cardiomyocytes.

Moderate hypothermia plays a major role in myocardial cell death as a result of hypoxia/reoxygenation (H/R) injury. However, few studies have investigated the molecular mechanisms of hypothermic cardioprotection. Several responses to stress and other cell functions are regulated by post­translational protein modifications controlled by small ubiquitin­like modifier (SUMO). Previous studies have established that high SUMOylation of proteins potentiates the ability of cells to withstand hypoxic­ischemic stress. The level to which moderate hypothermia affects SUMOylation is not fully understood, as the functions of SUMOylation in the heart have not been studied in depth. The aim of the present study was to investigate the effect of moderate hypothermia (33˚C) on the protective functions of SUMOylation on myocardial cells. HL­1 and H9c2 cells were treated with the hypoxia­mimetic chemical CoCl2 and complete medium to simulate H/R injury. Hypothermia intervention was then administered. A Cell Counting kit­8 assay was used to analyze cell viability. Mitochondrial membrane potential and the generation of reactive oxygen species (ROS) were used as functional indexes of mitochondria dysfunction. Bcl­2 and caspase­3 expression levels were analyzed by western blotting. The present results suggested that moderate hypothermia significantly increased SUMO1 and Bcl­2 expression levels, as well as the mitochondrial membrane potential, but significantly decreased the expression levels of caspase­3 and mitochondrial ROS. Thus, moderate hypothermia may enhance SUMOylation and attenuate myocardial H/R injury. Moreover, a combination of SUMOylation and moderate hypothermia may be a potential cardiovascular intervention.

Homocysteine, vitamin B12, and folate levels in patients with multiple sclerosis in Chinese population: A case-control study and meta-analysis.

BACKGROUND: Current studies suggested discrepancies on the correlations between multiple sclerosis (MS) and blood levels of homocysteine (Hcy), vitamin B12 (VB12), and folate. We performed a case-control study and meta-analysis to help resolve the controversy of these lab values in Chinese patients with MS. METHODS: We recruited 80 Chinese MS patients, 86 age/sex matched neurological controls (patients with peripheral vertigo or sleep disorders), and 80 age- and sex-matched healthy controls. Serum Hcy levels were measured using flourimetric high-performance liquid chromatography, serum levels of VB12 and folate using immune assay. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed was conducted for case-control studies with pure Chinese populations published up to March 16, 2019. The effective size was estimated by the pooled standardized mean difference (SMD) and associated 95% confidence interval (CI). RESULTS: The case-control study results suggest higher Hcy levels (mean ± SD) and frequency of hyperhomocysteinemia in the Chinese MS cases than control groups (all p < 0.001), lower for VB12 levels (mean ± SD, p = 0.043 or 0.039). No significant difference was observed for levels of folate (mean ± SD, both p > 0.05), and for frequency of folate or VB12 deficiency (all p > 0.05). Analysis of pooled SMDs and 95% CIs suggested increased Hcy levels in Chinese MS patients (SMD: 2.31, 95% CI: 1.33-3.28, p < 0.001), and in relapsing or remitting cases relative to controls (SMD: 0.94 or 0.85, 95% CI: 0.49-1.39 or 0.35-1.34, both p < 0.001). The meta-analysis results also suggested reduced VB12 levels in Chinese MS patients (SMD: -0.30, 95% CI: -0.46-0.14, p < 0.001), and in relapsing MS patients compared to controls (SMD: -0.31, 95% CI: -0.47-0.15, p < 0.001), while no statistical difference for cases in remission. No significant difference was observed for levels folate in all comparisons. CONCLUSION: Patients with MS tend to have increased blood Hcy levels compared to controls. MS patients of Chinese origin and those in relapse may have decreased levels of VB12. Hcy and VB12 may contribute to pathogenesis of the disease, and VB12 may correlate with MS relapse.

BDNF Val66Met polymorphism and cognitive impairment in Parkinson's disease-a meta-analysis.

BACKGROUND: Conflicting results identifying the association between Brain-derived neurotrophic factor (BDNF) polymorphism, Val66Met, and cognitive impairment in Parkinson's disease (PD) have been reported. METHODS AND RESULTS: To clarify whether Val66Met is related to cognitive impairment in PD, we carried out this meta-analysis by searching literature from PubMed, Web of Science, and Embase databases regarding this polymorphism. Six eligible studies involving 1467 PD patients were included in this meta-analysis. Our results showed statistically significant association between Val66Met and risk of cognitive impairment in PD patients in additive model (Met/Met vs. Val/Val: OR 3.82, 95%CI 1.32 to 11.08, p = 0.01) and recessive model (Met/Met vs. Val-carrier: OR 3.81, 95%CI 1.38 to 10.53, p = 0.01) except for dominant model. CONCLUSIONS: Our meta-analysis implicates Val66Met BDNF polymorphism may be associated with Parkinson's disease cognitive impairment, further well-designed studies with larger populations are required to validate these results owing to the limited research.

Vinpocetine in the treatment of poststroke cognitive dysfunction: A protocol for systematic review and meta-analysis.

BACKGROUND: Previous clinical trials have reported that vinpocetine can be used for the treatment of cognitive dysfunction. However, its efficacy is still inconclusive. In this systematic review study, we aim to assess its efficacy and safety for the treatment of poststroke cognitive dysfunction (PSCD). METHODS: We will search the following electronic databases from the inception to the present to evaluate the efficacy and safety of vinpocetine for patients with PSCD. These databases include CENTRAL, EMBASE, MEDILINE, CINAHL, AMED, and four Chinese databases. All randomized controlled trials (RCTs) of vinpocetine for PSCD will be considered for inclusion without the language restrictions. The methodological quality of all included RCTs will be evaluated by the Cochrane risk of bias tool. The 95% confidence intervals will be utilized to calculate the continuous data, the mean difference or standard mean difference, and dichotomous data with risk ratio. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed journals. Its results may provide important evidence for the clinical practice, as well as the future studies. It does not require ethical approval, because this systematic review will not involve the individual data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018115224.

[Association between SNP rs12740374 and acute ischemic stroke in Chinese Han population].

OBJECTIVE: To investigate the association between single nucleotide polymorphism (SNP) rs12740374 and acute ischemic stroke in Chinese Han population. METHODS: All subjects (778 ischemic stroke patients and 602 controls) were genotyped using ligation detection reaction (LDR). We analyzed the differences among all genotypes in two groups, as well as the association between rs12740374 and low-density lipoprotein cholesterol (LDL-C). RESULTS: All three genotypes (GG, GT, TT) of rs12740374 were found in both stroke and control group. After adjusting for risk factors, although there was a trend that participants with a minor allele T of rs12740374 (GT/TT) had lower LDL-C concentration, no significant association was found between rs12740374 and ischemic stroke, and also no significant association between different genotypes and LDL-C was found. CONCLUSION: SNPs of rs12740374 was not significantly associated with ischemic stroke in the Chinese Han population.

Association between two functional fibrinogen-related polymorphisms and ischemic stroke: a case-control study.

OBJECTIVES: Currently, there is a debate regarding the roles of two functional fibrinogen-related variants (rs6050 and rs1800790) and ischemic stroke (IS). MATERIALS AND METHODS: A total of 1402 subjects (834 cases and 568 controls) were genotyped for single-nucleotide polymorphisms rs6050 and rs1800790 with the ligation detection reaction method. RESULTS: We found that the homozygous minor allele genotype (GG) of rs6050 significantly increased IS risk by 66%, whereas that of rs1800790 reduced risk by 59% (rs6050: odds ratio [OR]=1.660, 95% confidence intervals [CI]: 1.141-2.415, p=0.008; rs1800790: OR=0.413, 95% CI: 0.228-0.747, p=0.003). After stratifying IS by three common subtypes, consistent results were found in IS cases with large-artery atherosclerosis (rs6050: OR=2.116, 95% CI: 1.327-3.376, p=0.002; rs1800790: OR=0.191, 95% CI: 0.085-0.430, p=0.000), and we also observed that the homozygous minor allele genotype of rs6050 increased risk by 86% in IS cases with cardioembolism (OR=1.859, 95% CI: 1.243-2.782, p=0.003). However, a paradox of association was shown between these two sites and fibrinogen levels. In haplotype analysis, we found that those with haplotype AA (major allele of rs6050 and minor allele of rs1800790) could reduce susceptibility to IS by 35% (OR=0.650, 95% CI: 0.493-0.858, p=0.002). CONCLUSION: Our study suggested that minor allele G of rs6050 is a significant risk factor, which can increase IS risk in the Chinese Han population, while minor allele A of rs1800790 and the haplotype AA lower such risk.

The functional SNP rs4376531 in the ARHGEF gene is a risk factor for the atherothrombotic stroke in Han Chinese.

The gene encoding RhoA guanine nucleotide exchange factor 10(ARHGEF10) has been reported to be a risk factor for atherothrombotic stroke (AS) in Japanese. The single-nucleotide polymorphism (SNP) rs4376531 in intron 16 on ARHGEF10 is associated with AS and may play a role in the disease pathology. In order to explore the nature of this association in greater detail and in a new ethnic group, we carried out a case-control study to determine whether the rs4376531 polymorphism in ARHGEF10 is a risk factor of AS in Han Chinese people. This study was carried out to assay the frequency of genotypes and alleles of SNP rs4376531 in ARHGEF10 in patients with ischemic stroke and healthy controls using the polymerase chain reaction and the restriction fragment length polymorphism (PCR-RFLP) technique. A total of 383 individuals with AS in West China Hospital and 214 unrelated healthy controls were recruited. The frequencies of the G allele and GG genotype of the rs4376531 polymorphism were higher in the patients with AS than in control individuals: frequency of G, 91.0% vs 83.4%, P<0.001; GG, 82.2% vs 67.8%, P<0.001. After adjusting for sex, age, and multiple cardiovascular risk factors, the homozygous GG genotype for this variant was associated with a higher risk of AS, with an adjusted odds ratio of 4.99 (95% CI, 2.55-7.81, P< 0.001). Our findings suggest that the rs4376531 polymorphism in the ARHGEF10 gene is a risk factor for AS in the Han Chinese population.