The association of cystathionine β synthase (CBS) T833C polymorphism and the risk of stroke: a meta-analysis

As results from published studies on the association of Cystathionine β Synthase (CBS) T833C genetic polymorphism with the risk of stroke are inconsistent, we performed a meta-analysis to summarize the possible association. Eligible studies published were searched for in PubMed, Elsevier Science Direct, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and the Chinese database, Wanfang. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for the association using fixed- or random-effect model. We identified 10 case-control studies including 2247 cases and 1813 controls for the present meta-analysis. Significant associations between CBS T833C genetic polymorphism and risk of stroke were observed in most genetic models (OR=1.57, 95% CI=1.02-2.41, p=0.039 for TC+CC vs. TT; OR=1.79, 95% CI=1.14-2.82, p=0.012 for CC vs. TT; OR=1.56, 95% CI=1.01-2.40, p=0.044 for TC vs. TT). Moreover, in the subgroup analysis based on ethnicity, significant associations were observed in most genetic models in Chinese but not in Caucasian. This meta-analysis provided evidence that CBS T833C genetic polymorphism was associated with increased risk of stroke, and the C allele probably acts as an important stroke risk factor.     

Interleukin-1A ?889C/T polymorphism and risk of Alzheimer’s disease: a meta-analysis based on 32 case–control studies

The Interleukin-1A (IL-1A) -889C/T polymorphism has been reported to be associated with Alzheimer's disease (AD) susceptibility, but the results of these previous studies have been inconsistent. The aim of this study was to explore whether the IL-1A -889C/T polymorphism confers susceptibility to AD. All studies published up to July 2011 on the association between the IL-1A -889C/T polymorphism and AD risk were identified by searching electronic databases PubMed, Embase and Alzgene. The association between the IL-1A -889C/T polymorphism and AD risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 32 case-control studies including 7,046 AD cases and 7,534 controls were eventually identified. Overall, positive associations of the IL-1A -889C/T polymorphism with AD risk were found in allele comparison T versus C (OR = 1.019, 95% CI= 1.027-1.198), recessive model TT versus CT + CC (OR = 1.278, 95% CI = 1.073-1.522) and dominant model TT + CT versus CC (OR = 1.102, 95% CI = 1.013-1.200). In subgroup analysis stratified by ethnicity, significant associations were demonstrated in Caucasians but not in Asians. In subgroup analysis according to the age of onset, no significant association was detected. The present meta-analysis suggests that the IL-1A is a candidate gene for AD susceptibility. The IL-1A -889C/T889C/T polymorphism may be a risk factor for AD in Caucasians. Further investigations taking the APOE ε4 status and other confirmed genetic factors and potential gene-gene and gene-environmental interactions into consideration for this polymorphism should be conducted.     

Association between the – 1562 C/T MMP-9 polymorphism and cerebrovascular disease in a Polish population

Background and purposeMatrix metalloproteinase 9 (MMP-9) is an endopeptidase degrading extracellular matrix. There is growing evidence that changes in extracellular matrix play an important role in vascular pathology, especially in cardiovascular and cerebrovascular disease. Previous studies have demonstrated that MMP-9 activity is controlled by –1562 C/T polymorphism. Genotypes with T allele (CT, TT) have higher enzymatic activity. Thus, this polymorphism could be responsible for the higher risk for cerebrovascular disease and death. The aim of this study was to assess the significance of MMP-9 polymorphism as a risk factor for cerebrovascular disease in a Polish population.Material and methodsA total of 775 consecutive patients with a diagnosis of cerebrovascular disease (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage) admitted to the Stroke Unit, Jagiellonian University, Krakow, Poland between 2000 and 2004 were studied and compared with 766 matched controls. The polymorphism was studied by polymerase chain reaction (PCR) and restricted enzyme digestion.ResultsAmong 418 patients with ischaemic stroke of various aetiologies and among 146 patients with primary intracerebral haemorrhage and 211 patients with subarachnoid haemorrhage due to ruptured intracranial aneurysm, statistical analysis did not show a significant difference between occurrence of CC, CT, TT genotypes or C and T alleles in patients with stroke of various aetiology compared with controls.ConclusionsWe found no association between the –1562 C/T MMP-9 polymorphism and ischaemic stroke, subarachnoid haemorrhage or spontaneous intracerebral haemorrhage in the studied Polish population.     

Recurrence after a first unprovoked cryptogenic/idiopathic seizure in children: a prospective study from São Paulo, Brazil

PURPOSE: To evaluate the recurrence risk after a first unprovoked seizure in a large population of children and adolescents of a developing country. METHODS: This prospective study was conducted at two tertiary hospitals, between September 1989 and August 1998. Children were enrolled if they had a first unprovoked cryptogenic/idiopathic seizure and maximal interval to the enrollment < or =90 days. EEG and computed tomography (CT) were performed in most patients. Potential predictors of recurrence were compared by using the Cox proportional hazards model in univariate and multivariate analyses. Survival analysis was performed by using the Kaplan-Meier curves. RESULTS: Two hundred thirteen children were included. Recurrence occurred in 34% of the patients, and mean time for recurrence was 12 months. Statistical analysis showed significance for seizure recurrence only for patients with abnormal EEGs. CT was performed in 182 patients, and abnormalities were found in 9.5%. Small calcifications were the most frequent finding, and this was not a predictor for recurrence. CONCLUSIONS: The risk of recurrence after a first unprovoked seizure in children from a developing country is similar to that found in developed countries. An abnormal EEG is a risk factor for seizure recurrence in children with a cryptogenic/idiopathic seizure. Calcifications on CT do not increase the risk of recurrence.     

Association between interleukin-1α C(−889)T polymorphism and Alzheimer’s disease: a meta-analysis including 12,817 subjects

Epidemiological studies have evaluated the association between interleukin-1 (IL-1)α C(?889)T polymorphism and Alzheimer’s disease (AD), but the results remain inconclusive. This meta-analysis was, therefore, designed to clarify these controversies. Systematic searches of electronic databases Embase, PubMed, and Web of Science as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.2) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were calculated. A total of 28 publications including 29 studies were involved. There was a significant association between IL-1α C(?889)T polymorphism and AD (for T allele vs. C allele: OR = 1.14, 95 % CI = 1.07–1.21; for T/T vs. C/C: OR = 1.39, 95 % CI = 1.18–1.63; for dominant model: OR = 1.13, 95 % CI = 1.04–1.22; and for recessive model: OR = 1.39, 95 % CI = 1.20–1.60). Significant association was found for Asians, Caucasians, and early-onset Alzheimer’s disease (EOAD) but for late-onset Alzheimer’s disease (LOAD). This meta-analysis indicates that there is a significant association between IL-1α C(?889)T polymorphism and AD as well as EOAD.     

Intense/obsessional interests in children with gender dysphoria: a cross-validation study using the Teacher’s Report Form

Objective

This study assessed whether children clinically referred for gender dysphoria (GD) show symptoms that overlap with Autism Spectrum Disorder (ASD). Circumscribed preoccupations/intense interests and repetitive behaviors were considered as overlapping symptoms expressed in both GD and ASD.

Methods

To assess these constructs, we examined Items 9 and 66 on the Teacher’s Report Form (TRF), which measure obsessions and compulsions, respectively.

Results

For Item 9, gender-referred children (n = 386) were significantly elevated compared to the referred (n = 965) and non-referred children (n = 965) from the TRF standardization sample. For Item 66, gender-referred children were elevated in comparison to the non-referred children, but not the referred children.

Conclusions

These findings provided cross-validation of a previous study in which the same patterns were found using the Child Behavior Checklist (Vanderlaan et al. in J Sex Res 52:213–19, 2015). We discuss possible developmental pathways between GD and ASD, including a consideration of the principle of equifinality.

     

Association of transforming growth factor-β1 gene C509T,G800A and T869C polymorphisms with intracerebral hemorrhage in North Indian Population: a case–control study

Transforming growth factor-β1 (TGF-β1) is a multifunctional pro-inflammatory cytokine involved in inflammation and pathogenesis of cerebrovascular disease. As per our knowledge, there is no published study investigating the association between variations within the TGF-β1 gene polymorphisms and risk of intracerebral hemorrhage (ICH). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A and T869C) polymorphisms, and their haplotypes with the risk of ICH in North Indian population. 100 ICH patients and 100 age- and sex-matched controls were studied. Genotyping was performed using SNaPshot method. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of ICH. Hypertension, diabetes, dyslipidemia, low socioeconomic status, smoking, physical activity were found to be associated with the risk of ICH. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy–Weinberg Equilibrium (HWE) in the ICH and control group. Adjusted conditional logistic regression analysis showed an independent association of TGF-β1 G800A (OR 9.07; 95 % CI 2.3–35.6; P = 0.002) and T869C (OR 5.1; 95 % CI 1.9–13.2; P = 0.001) with the risk of ICH under dominant model. Haplotype analysis showed that C509-G800-C869 and C509-A800-C869 haplotypes were significantly associated with the increased risk of ICH. C509T and T869C were in strong linkage disequilibrium (D’ = 0.53, r ² = 0.23). Our results suggest that TGF-β1 (G800A, T869C) gene polymorphisms and their haplotypes are significantly associated with the risk of ICH in North Indian population. Further prospective studies with large sample size are required for independent validation. Our findings could be helpful in identifying individuals at increased risk for developing ICH.     

Commentary: Sports participation at 4 years old? Thoughts on mental health-risk trajectories in the longitudinal study of Australian children – a commentary on Vella et al. (2018)

Vella and colleagues (this issue) report on children in the kindergarten cohort of the Longitudinal Study of Australian Children (LSAC) study, using predictors from age 4 years to identify six trajectories of mental health risk from ages 4–12. Somewhat surprisingly, they find that among some predictable candidates for risk, such as sex and family income, that sports participation at age four emerges as a novel predictor of low difficulty with respect to mental health trajectories across the next 8 years. Is this a case of mens sana in corpore sano? Or is sports participation, that is, swimming, dancing, gymnastics, and team sports, a proxy for other factors? What can the various predictors and the trajectories of mental health risk from this longitudinal study tell us about interventions to reduce risk?     

TLR9 −1237 T/C and TLR2 −194 to −174 del polymorphisms and the risk of Parkinson’s disease in the Greek population: a pilot study

Toll-like receptors (TLRs) are important mediators of inflammatory responses by recognition of many pathogen-related molecules and endogenous proteins related to immune activation. Accumulating data have recently pointed out the role of neuroinflammation in Parkinson’s disease (PD) pathogenesis. In the present study, we investigated the potential role of the TLR9 ?1237 T/C and TLR2 ?194 to ?174 del polymorphisms in PD. We studied a total of 333 individuals, 215 Greek patients with sporadic PD and 118 control subjects, using a polymerase chain reaction–restriction fragment length polymorphism method. No statistically significant differences were found between PD patients and control subjects for the TLR9 ?1237 T/C genotypes or alleles. Regarding the TLR2 ?196 to ?174 del polymorphism, the del/del genotype and the del allele were overrepresented in the PD group compared to controls, however, this result did not reach statistical significance (P = 0.087). Further studies investigating the TLR-inflammatory background of PD are awaited to provide important insight into the aetiology of the disease.     

Accurate determination of blood–brain barrier permeability using dynamic contrast-enhanced T1-weighted MRI: a simulation and in vivo study on healthy subjects and multiple sclerosis patients

Dynamic contrast-enhanced magnetic resonance imaging (DCE–MRI) is increasingly used to estimate permeability in situations with subtle blood–brain barrier (BBB) leakage. However, the method''s ability to differentiate such low values from zero is unknown, and no consensus exists on optimal selection of total measurement duration, temporal resolution, and modeling approach under varying physiologic circumstances. To estimate accuracy and precision of the DCE–MRI method we generated simulated data using a two-compartment model and progressively down-sampled and truncated the data to mimic low temporal resolution and short total measurement duration. Model fit was performed with the Patlak, the extended Tofts, and the Tikhonov two-compartment (Tik-2CM) models. Overall, 17 healthy controls were scanned to obtain in vivo data. Long total measurement duration (15 minutes) and high temporal resolution (1.25 seconds) greatly improved accuracy and precision for all three models, enabling us to differentiate values of permeability as low as 0.1 ml/100 g/min from zero. The Patlak model yielded highest accuracy and precision for permeability values <0.3 ml/100 g/min, but for higher values the Tik-2CM performed best. Our results emphasize the importance of optimal parameter setup and model selection when characterizing low BBB permeability.     

New perspectives on neurochemical effects of amantadine in the brain of parkinsonian patients: a PET – [<Superscript>11</Superscript>C]raclopride study

Summary. Amantadine, is a non competitive NMDA receptors antagonist that has been proved beneficial in Parkinson's disease. However its mechanism of action at therapeutic doses is still under discussion. Aim of this study was to evaluate the effect of repeated administration of amantadine on striatal dopaminergic system by measuring [¹¹C]raclopride binding to striatal D₂ dopamine receptors, in patients with moderate idiopathic Parkinson's disease. Eight patients completed the study undergoing a PET scan, before and after 10–14 days treatment with Amantadine (200 mg/day). Patients were on treatment with L-DOPA, which was suspended 1 night before each PET scans, and free from dopaminergic agonists, anticholinergic and antidepressants. Amantadine treatment significantly increased [¹¹C-]Raclopride binding (caudate: 10% p = 0.04; putamen 11% p = 0.01). A slight reduction (−7.3%, p = 0.062) of UPDRS total scores was also observed. The increased availability of striatal D₂ receptors, is likely to be caused by drug induced modification of receptors expression. This hypothesis is consistent with previous experiments, indicating an increase in striatal D₂ receptors in rats treated with amantadine or other non competitive NMDA antagonists and suggests that the neo-synthesis of D₂ receptors may represent a reinforcing mechanism of drug efficacy. Received October 17, 2001; accepted January 3, 2002 Published online June 28, 2002     

Combined Effects of the C161T and Pro12Ala PPARγ2 Gene Variants with Insulin Resistance on Metabolic Syndrome: A Case–Control Study of a Central Tunisian Population

We investigated the synergism between variants at the PPARγ locus (C161T and Pro12Ala polymorphisms) with insulin resistance on metabolic syndrome (MS). Five hundred twenty-two subjects were investigated for biochemical and anthropometric measurements. The diagnosis of MS was based on the IDF definition (2009). The HOMA 2 was used to determine HOMA-β, HOMA-S, and HOMA-IR from FPG and FPI concentrations. PCR-RFLP was performed for DNA genotyping. We showed that carriers of the Pro/Pro had a significantly higher FPG, FPI, and HOMA-IR. In addition, Pro/Pro subjects also display reduced HOMA-β and HOMA-S together compared to X/Ala (Pro/Ala and Ala/Ala) subjects. Furthermore, subjects with C/C have a significantly lower FPG, FPI, and HOMA-IR and higher HOMA-S compared to X/T (C/T and T/T) subjects. The C/C genotype carriers with an Ala allele group had significantly reduced FPG, FPI, HOMA-IR, and TG and elevated HOMA-S and HOMA-β than the different genotype combinations. We suggest that the haplotype composed of the C/C genotype carriers with an Ala allele of PPARγ2 group enhances susceptibility to the MS in a central Tunisian population.     

Association between polymorphism in the promoter region of <Emphasis Type="Italic">Interleukin 6</Emphasis> (-174 G/C) and risk of Alzheimer’s disease: a meta-analysis

Studies of the relationship between Alzheimer’s disease (AD) and polymorphism in the promoter region of Interleukin 6 (IL-6) -174 G/C have reported inconsistent results. To assess the association between IL-6 -174 G/C promoter polymorphism and AD risk, a meta-analysis containing 3,101 AD cases and 3,860 controls from 18 case–control studies was performed. There were 16 studies involving Europeans and 2 studies involving non-Europeans. The combined results showed significant differences in recessive model [CC versus GC + GG, odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.54–0.90] and heterozygote comparison (CC versus GC, OR = 0.76, 95% CI = 0.60–0.96) on the basis of all studies. On subgroup analysis by ethnicity, similarly significant differences in recessive model (CC versus GC + GG) were found in both Europeans and non-Europeans, but significant difference in heterozygote comparison (CC versus GC) was found only in non-Europeans. In conclusion, there were statistically significant differences in genotype distribution of IL-6 -174 G/C between AD cases and controls in recessive model (CC versus GC + GG). Genotype CC of IL-6 -174 G/C could decrease the risk of AD. Further studies with large sample size, especially in subgroup analysis, should be done.