Effects of Gentiana delavayi Flower Extract on APP Processing in APP/PS1 CHO Cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana delavayi Franch. (Gentianaceae) as an ethnomedicinal plant contains a variety of effective active ingredients and exhibits diverse pharmacological actions, such as hepatoprotective, anti-inflammatory and central nervous system effects. In this study we investigated the influence of G. delavayi flower extract on amyloid precursor protein (APP) processing at molecular and cellular levels. APP/PS1 Chinese hamster ovary (CHO) cells were treated with chloroform extract of G. delavayi flower in different concentrations for 24 h. Concentrations of amyloid ß (Aß) 40 and Aß42 in the cell supernatant and activity of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), BACE2, and cathepsin D were determined. The expression of APP and neprilysin (NEP) within the cell were further determined. Compared with the control group, the levels of Aß40 and Aß42 declined notably and the activity of BACE1 was inhibited significantly in the APP/PS1 CHO cells after treatment with the chloroform extract of G. delavayi flower. Although the activities of BACE2 and cathepsin D were not changed, the expression of Aß degrading enzyme NEP increased remarkably. Our experiments have clearly showed that the chloroform extract of G. delavayi flower inhibits the generation of ß-amyloid by specifically inhibiting ß-secretase and increases the expression of NEP which fastens the degradation of Aß, exhibiting the effect of decreasing Aß accumulation in APP/PS1 CHO cells. These results suggest that the active components from the chloroform extract of G. delavayi flower have a further prospect to be developed as potential anti-Aß drug.

The effect of transient receptor potential vanilloid 4 on the intestinal epithelial barrier and human colonic cells was affected by tyrosine-phosphorylated claudin-7.

TRPV4 is a type of nonselective cation channel, and activation of TRPV4 in the gastrointestinal tract causes experimental colitis in mice. A previous study found that tyrosine-phosphorylated claudin-7 is increased in experimental colitis. The relationship between tyrosine-phosphorylated claudin-7 and TRPV4 remains undefined. In the present study, we developed a claudin-7 mutant by replacing tyrosine with glutamic acid at position 210, named cld7-Y210E colonic cells. We found that activation of TRPV4 by GSK1016790A increased the permeability of control colonic cell monolayers, which was decreased by the TRPV4 antagonist HC067047. In monolayers of cld7-Y210E colonic cells, no differences in permeability were found between GSK1016790A and HC067047 treatments. GSK1016790A increased the aggregation of claudin-7 at the cell membrane in control colonic cells, and the effect was diminished by HC067047. In cld7-Y210E colonic cells, neither GSK1016790A nor HC067047 apparently changed the aggregation of claudin-7. Neither GSK1016790A nor HC067047 altered the TRPV4 protein level in vector colonic cells. In cld7-wild colonic cells, GSK1016790A did not alter the TRPV4 protein level, while HC067047 increased the TRPV4 protein level. The TRPV4 protein level was increased in cld7-Y210E colonic cells, decreased by GSK1016790A and further decreased by HC067047. Calcium influx was not significantly changed in the control colonic cells treated with GSK1016790A. However, GSK1016790A significantly increased calcium influx in cld7-Y210E colonic cells. We concluded that tyrosine-phosphorylated claudin-7 affects the TRPV4-modulated intestinal epithelial barrier, TRPV4-mediated calcium influx, and the protein expression of TRPV4 in human colonic cells. We suggest that tyrosine-phosphorylated claudin-7 affects the TRPV4-modulated intestinal epithelial barrier, which might be related to TRPV4 expression and TRPV4-mediated calcium influx.

A novel, potent, and orally bioavailable thiazole HCV NS5A inhibitor for the treatment of hepatitis C virus.

A medicinal chemistry program based on the small-molecule HCV NS5A inhibitor daclatasvir has led to the discovery of dimeric phenylthiazole compound 8, a novel and potent HCV NS5A inhibitor. The subsequent SAR studies and optimization revealed that the cycloalkyl amide derivatives 27a-29a exhibited superior potency against GT1b with GT1b EC50 values at picomolar concentration. Interestingly, high diastereospecificity for HCV inhibition was observed in this class with the (1R,2S,1'R,2'S) diastereomer displaying the highest GT1b inhibitory activity. The best inhibitor 27a was found to be 3-fold more potent (GT1b EC50 = 0.003 nM) than daclatasvir (GT1b EC50 = 0.009 nM) against GT1b, and no detectable in vitro cytotoxicity was observed (CC50 > 50 µM). Pharmacokinetic studies demonstrated that compound 27a had an excellent pharmacokinetic profiles with a superior oral exposure and desired bioavailability after oral administration in both rats and dogs, and therefore it was selected as a developmental candidate for the treatment of HCV infection.

Intramolecular Self-Enhanced Nanochains Functionalized by an Electrochemiluminescence Reagent and Its Immunosensing Application for the Detection of Urinary ß2-Microglobulin.

In this study, polyethylenimine (PEI) is discovered to possess a noticeable amplification effect for the electrochemiluminescence (ECL) of N-(aminobutyl)-N-(ethylisoluminol) (ABEI); thus, a novel self-enhanced ECL reagent (ABEI-PEI) is prepared by covalent cross-linking. Because of the shortened electron-transfer path and reduced energy loss, the intramolecular ECL reaction between ABEI and PEI exhibited enhanced luminous efficiency compared with the traditional intermolecular ECL reaction. Owing to the amine-rich property of PEI, abundant ABEI could be immobilized on the molecular chains of PEI to strengthen the luminous intensity of ABEI-PEI. On account of the reducibility of remaining amino groups, ABEI-PEI, as the self-enhanced ECL reagent, has also been chosen as a reductant and stabilizer for in situ preparation of Au@Ag nanochains (Au@AgNCs) which has the catalytic activity for the ECL reaction. Moreover, using ABEI-PEI as a template to directly prepare Au@AgNCs realizes the immobilization of the ECL reagent with large amounts. Meanwhile, in virtue of the electropositivity of ABEI-PEI-capped Au@AgNCs (ABEI-PEI-Au@AgNCs), polyacrylic acid (PAA) with electronegativity is pervaded on the surface of nanochains and further chelates with Co2+ to form an ABEI-PEI-Au@AgNCs-PAA/Co2+ complex, which could introduce Co2+ as a catalyst to promote H2O2 decomposition and thus oxidize ABEI to produce an enhanced ECL signal. Here, the obtained self-enhanced ABEI-PEI-Au@AgNCs-PAA/Co2+ complex is utilized to capture the detection antibody (Ab2). According to sandwiched immunoreactions, a sensitive ECL immunosensor is constructed for the detection of ß2-microglobulin with a wide linearity from 0.01 pg mL-1 to 200 ng mL-1 and a detection limit of 3.3 fg mL-1.

A prospective study of psychological resilience and depression among left-behind children in China.

This prospective study examined the longitudinal effects of psychological resilience on depression in a Chinese sample of left-behind children. A total of 386 left-behind children completed both a baseline and a 1-year follow-up survey. The prevalence of depression at the baseline and 1-year follow-up was 12.7 and 8.5 per cent, respectively. Multivariate analysis revealed that older age and baseline depressive symptoms were positively associated with follow-up depression, while psychological resilience and quality of life were negatively related to follow-up depression. Our findings provided preliminary evidence that higher psychological resilience was a significantly protective factor of developing depression among left-behind children.

A Potent, Selective, and Orally Bioavailable HCV NS5A Inhibitor for Treatment of Hepatitis C Virus: (S)-1-((R)-2-(Cyclopropanecarboxamido)-2-phenylacetyl)-N-(4-phenylthiazol-2-yl)pyrrolidine-2-carboxamide.

Starting from the initial lead 4-phenylthiazole 18, a modest HCV inhibitor (EC50 = 9440 nM), a series of structurally related thiazole derivatives has been identified as a novel chemical class of potent and selective HCV NS5A inhibitors. The introduction of a carboxamide group between the thiazole and pyrrolidine ring (42) of compound 18 resulted in a dramatic increase in activity (EC50 = 0.92 nM). However, 42 showed only moderate pharmacokinetic properties and limited oral bioavalability of 18.7% in rats. Further optimization of the substituents at the 4-position of the thiazole ring and pyrrolidine nitrogen of the lead compound 42 led to the identification of compound 57, a highly potent and selective NS5A inhibitor of HCV (EC50 = 4.6 nM), with greater therapeutic index (CC50/EC50 > 10000). Pharmacokinetic studies revealed that compound 57 had a superior oral exposure and desired bioavailability of 45% after oral administration in rats.

The risk and protective factors in the development of childhood social anxiety symptoms among Chinese children.

The aim of this study was to explore the change and associated risk and protective factors of social anxiety symptoms among Chinese children. A 2-year longitudinal study was performed in a general primary and secondary school population in Anhui Province, China including 816 children in grades 3, 4, and 7. Children's social anxiety symptoms were assessed using the Social Anxiety Scales for Children (SASC) at three assessments. The overall prevalence of children's elevated social anxiety symptoms ranged from 15.2% to 16.4% across three assessments. Children's overall mean SASC scores were 5.6 (SD =3.7), 5.3 (SD =3.8), and 5.3 (SD =4.1) at three assessments, respectively, but the difference was not statistically significant. However, children's social anxiety symptom levels and change among different subgroups was not stable across 2-year follow-up. Multivariable logistic regression analysis indicated that age, severe family dysfunction, quality of life, positive coping, negative coping, depressive symptoms and self-esteem were predictive factors for childhood elevated social anxiety symptoms. The findings suggested that the overall social anxiety symptoms showed a relatively stable pattern over time. The identified risk and protective factors may provide scientific evidence for school, family, and health authorities to conduct necessary intervention.

Associations of Angiotensin-Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta-Analysis.

There have been numerous studies concerning the associations of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D), angiotensin II receptor 1 (AT1R) gene A1166C, and endothelial nitric oxide synthase (eNOS) gene 4b/a polymorphisms with risk of pregnancy hypertensive disorders (PHDs). However, the results are inconsistent. A total of 83 eligible studies (10,354/18,446 cases/controls) were included in this meta-analysis. Pooled odds ratios with corresponding 95% confidence intervals were used to calculate these associations. The effects of ethnicity and types of PHDs were also considered. Results showed significant associations between the ACE gene polymorphism and PHDs in all of the populations except that in Africa. The associations also existed in AT1R, eNOS gene polymorphism and PHDs in part of the gene models in the overall population. These results indicated the ACE gene polymorphism was associated with an increased risk of PHDs, whereas the eNOS and AT1R gene polymorphism only have increased susceptibility to PHDs in part of the gene models.

Association between apolipoprotein E gene polymorphism and depression.

We performed an updated meta-analysis to obtain a more precise estimation of the relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility to depression, as previous reports have been inconsistent. Twenty studies with 2286 depression patients and 3845 controls were included. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association between ApoE gene polymorphism and depression using a random effects model. Results showed a significant association between ApoE gene polymorphism and susceptibility to depression in the overall population (ε2/ε3 genotype versus ε3/ε3: OR 0.76, 95% CI 0.59-0.99). Subgroup analyses indicated an association in the Caucasian population (ε2 allele versus ε3: OR 0.75, 95% CI 0.58-0.97) as well as in late-life depression (LLD) patients (ε3/ε4 genotype versus ε3/ε3: OR 1.34, 95% CI 1.07-1.68, and ε4 allele versus ε3: OR 1.30, 95% CI 1.06-1.59). We concluded that the ε2/ε3 genotype likely provided a protective effect against depression in the overall population and the ε2 allele acted as a protective factor for depression in the Caucasian population while the ε4 allele and ε3/ε4 genotype were associated with an increased risk of depression in the LLD subjects.

Children in rural China enjoyed a significant increase in quality of life from 2009 to 2011.

AIM: Little is known about the long-term change in quality of life (QoL) among children in rural China. This study longitudinally examined changes and predictors of QoL among children in one rural county between 2009 and 2011. METHODS: We interviewed 816 children from seven to 16 years of age in 2009 and 2011 using a range of QoL tools. Multivariate forward stepwise linear regression analysis was used to examine the relationships between follow-up QoL and socio-demographic, family environment and psychosocial factors. RESULTS: Overall QoL scores improved significantly from 71.1 ± 14.6 to 72.8 ± 16.3 (p = 0.005). QoL was positively related to annual family income (ß = 0.14, p < 0.001) and baseline QoL (ß = 0.21, p < 0.001) and negatively related to older age (ß = -0.19, p < 0.001), being female (ß = -0.08, p = 0.011), being left in the care of family members by working parents (ß = -0.09, p = 0.004), negative coping styles (ß = -0.10, p = 0.005) and depression (ß = -0.11, p = 0.006). CONCLUSION: Quality of life significantly improved among children in rural China over a two-year period from 2009 to 2011. It was positively related to annual family income and baseline QoL and negatively related to older age, being female, being left in the care of family members by working parents, negative coping styles and depression.

Prevalence of suicidal ideation and associated factors among HIV-positive MSM in Anhui, China.

The aim of this study was to investigate the prevalence and factors associated with suicidal ideation among HIV-positive men who have sex with men (MSM) in Anhui, China. A cross-sectional study was conducted to recruit HIV-positive MSM in Anhui, China. A total of 184 HIV-positive MSM gave informed consent and completed the interview. Correlates of suicidal ideation were assessed using multivariable logistic regression. Fifty-seven (31%) of HIV-positive MSM had suicidal ideations within six months before the interview. Multivariable analyses showed that learning of their HIV status in the past 12 months (adjusted odds ratio (AOR) = 3.4, 95% CI = 1.6-7.3), perceived HIV stigma (AOR = 2.4, 95% CI = 1.1-5.2), depression symptoms (AOR = 2.6, 95% CI = 1.1-5.9) and anxiety symptoms (AOR = 2.7, 95% CI = 1.2-6.1) were significantly associated with the suicidal ideation among HIV-positive MSM. The results indicated that suicidal ideation was common among HIV-positive MSM in Anhui, China. There is an urgent need to establish psychological counselling services among HIV-positive MSM in China. Targeting of these potential risk factors could be an effective approach to reduce the suicide risk among this high-risk subgroup by the implementation of early intervention measurements.

Change and associated factors of self-esteem among children in rural China: A two-year longitudinal study.

Childhood has been targeted as an especially important period for self-esteem formation. The aim of this study is to examine the change and associated factors of self-esteem among children in rural China. A two-year longitudinal study was conducted with a general elementary and secondary school population in Anhui Province, China including 816 children aged between 7 and 16 years. Generalized estimating equation (GEE) was used to examine relationships between low self-esteem and socio-demographic, family environment, and psychosocial factors. On average, self-esteem level among children was increased across three assessments. Multivariable analysis (GEE) showed that low self-esteem in children was clearly associated with male gender (OR = 1.45, 95%CI = 1.12-1.89), moderate and severe family dysfunction (OR = 1.88, 95%CI = 1.40-2.51; OR = 1.88, 95%CI = 1.25-2.83, respectively), quality of life (OR = .97, 95%CI = .96-.98), depression (OR = 1.89, 95%CI = 1.32-2.70), anxiety (OR = 2.05, 95%CI = 1.51-2.77), positive coping styles (OR = .91, 95%CI = .89-.94), and negative coping styles (OR = 1.05, 95%CI = 1.03-1.07). Self-esteem is a dynamic rather than a static construct during childhood. Low self-esteem among children was associated with a number of socio-demographic, family environment, and psychosocial factors. Further studies exploring the pathways and mechanisms by which the effect of these factors impact on self-esteem among children are warranted.

Effects of repetitive transcranial magnetic stimulation on synaptic plasticity and apoptosis in vascular dementia rats.

This study aims to determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) protects pyramidal cells from apoptosis and promotes hippocampal synaptic plasticity in a vascular dementia (VaD) rat model. Following establishment of a VaD rat model using two-vessel occlusion (2VO), learning and memory were evaluated via the Morris Water Maze (MWM), hippocampal CA1 neuron ultrastructure was examined via electron microscopy, and hippocampal synaptic plasticity was assessed by long-term potentiation (LTP). Western blot was used to detect the expression of N-methyl-d-aspartic acid receptor 1 (NMDAR1), Bcl-2, and Bax. Compared with VaD group, rats treated with low-frequency rTMS had reduced-escape latencies, increased swimming time in the target quadrant (P<0.05), and significantly less synaptic structure damage. LTP at hippocampal CA3-CA1 synapses was enhanced (P<0.05). Low-frequency rTMS significantly up-regulated NMDAR1 and Bcl-2 expression and down-regulated Bax expression. Low-frequency rTMS improves learning and memory, protects the synapse, and increases synaptic plasticity in VaD model rats. Increased Bcl-2 expression and reduced Bax expression may be a novel protective mechanism of low-frequency rTMS treatment for VaD.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis.

Previous studies examining the possible role of the methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the development of schizophrenia (SZ) and bipolar disorder (BPD) have provided inconclusive findings, this meta-analysis was therefore designed to get a more reliable assessment. A total of 38 articles were identified through a search of electronic databases, up to 27 February 2014. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated using random effects models. Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT + CC: OR = 1.34, 95% CI: 1.18-1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR = 1.26, 95% CI: 1.00-1.59). Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations, but not for the white. MTHFR A1298C was significant associated with SZ, the highest OR for the dominant model (OR = 1.13, 95% CI: 1.03-1.24). Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups. We conclude that MTHFR polymorphism is associated with SZ and BPD among Asian, African populations, but not the white.

Association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and essential hypertension: a systematic review and meta-analysis.

OBJECTIVE: Many studies have investigated the role of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T/A1298C polymorphisms in essential hypertension (EH), but results are inconclusive. The purpose of this meta-analysis was to clarify the effects of MTHFR C677T/A1298C polymorphisms on the risk of EH. METHODS: Electronic databases were searched to identify relevant studies published until January 2014. Data were extracted by two independent authors. Odds ratios (ORs) with 95%confidence intervals (CIs) were used to assess the association between MTHFR C677T/A1298C polymorphisms and the risk of EH using random effect models or fixed effect models. Finally,30 studies with 5207 cases and 5383 controls were included for C677T polymorphism and 6 studies with 1009 cases and 994 controls were included for A1298C polymorphism. RESULTS: Meta-analysis results indicated that MTHFR C677T polymorphism contributed to an increased risk of EH (for T vs. C: OR=1.30, 95%CI=1.18­1.43; for TT+CT vs. CC: OR=1.34, 95%CI=1.24­1.46; for TT vs. CC: OR=1.62, 95%CI=1.32­1.99; for TT vs. CT+CC: OR=1.41, 95%CI=1.26­1.59). However, no significant association was detected between MTHFR A1298C polymorphism and the risk of EH. CONCLUSION: This meta-analysis supports that MTHFR C677T polymorphism plays a role in developing EH. MTHFR A1298C polymorphism may not be associated with an increased risk of EH. Further large and well-designed studies are warranted to confirm these findings.

Association of microtubule associated protein tau/Saitohin (MAPT/STH) MAPT_238bp/STH Q7R polymorphisms and Parkinson's disease: A meta-analysis.

BACKGROUND: The association between the extended tau haplotype (H1) and susceptibility to Parkinson's disease (PD) was controversial in previous studies. Therefore, we performed this meta-analysis to determine whether the additional polymorphisms in MAPT_238bp and STH Q7R which both included in H1 are associated with PD. METHODS: 19 studies were identified by a search of PubMed, PDGENE, Elsevier, Springer Link, CBM (Chinese Biomedical Database), CNKI (Chinese National Knowledge Infrastructure), VIP (Chinese), and Wanfang (Chinese) databases, up to May 2014. Additionally, manual retrieval of the references of identified articles was performed. Odds ratios (ORs) with 95% confidence interval (CI) were calculated using random effects model or fixed effects model based on the between-study heterogeneity. The subgroup analyses were performed by the ethnicity. All the statistical tests were conducted using Stata 9.0. RESULTS: Both of MAPT_238bp/STH Q7R polymorphisms had a significant association with PD risk in all genetic models. Subgroup analyses by ethnicity showed that the association between MAPT_238bp polymorphism and PD existed in Caucasian populations. CONCLUSIONS: The results of this meta-analysis suggested that MAPT_238bp/STH Q7R polymorphisms might modulate the risk of PD susceptibility. Certainly, additional well-designed studies are required to confirm these findings.

Cytochrome P450 1A1 (CYP1A1) polymorphism and susceptibility to esophageal cancer: an updated meta-analysis of 27 studies.

Cytochrome P450 1A1 (CYP1A1) polymorphisms are known to play a crucial role in the development and metastasis of malignant diseases including esophageal cancer. However, the results of previous studies investigating the association between CYP1A1 polymorphisms and esophageal cancer risk have been inconsistent. This meta-analysis of 27 eligible studies, encompassing 4,215 esophageal cancer cases and 6,339 control subjects, pooled the odds ratios (ORs) with corresponding 95 % confidence intervals (95 % CI) to assess this association. The effects of ethnicity (Caucasian and Asian) and histopathology type (esophageal squamous cell carcinoma and esophageal adenocarcinoma) were considered in subgroup analyses. A significant association was observed between the CYP1A1 Ile/Val gene polymorphism and esophageal cancer in all of the genetic models (Ile/Val vs. Ile/Ile, OR = 1.41, 95 % CI = 1.25-1.58; Val/Val vs. Ile/Ile, OR = 1.94, 95 % CI = 1.34-2.82; Ile/Val + Val/Val vs. Ile/Ile, OR = 1.49, 95 % CI = 1.33-1.66). The subgroup analysis based on ethnicity showed that the association between the CYP1A1 Ile/Val polymorphism and esophageal cancer existed in Asian and Caucasian populations. However, no association was observed between the CYP1A1 MspI polymorphism and esophageal cancer in either subgroup or in the overall population. These results suggested that the CYP1A1 Ile/Val polymorphism was associated with an increased risk of esophageal cancer, whereas the CYP1A1 MspI polymorphism may not have increased susceptibility to esophageal cancer. Further studies are required to confirm these findings.

Polymorphisms in FZD3 and FZD6 genes and risk of neural tube defects in a northern Han Chinese population.

Neural tube defects (NTDs) are the most common and severe malformations of the central nervous system. The association of single nucleotide polymorphisms (SNPs) of the Frizzled 3 (FZD3) and Frizzled 6 (FZD6) genes and NTDs in the Han population of northern China was principally studied. One synonymous SNP (rs2241802) in FZD3 gene and three nonsynonymous SNPs (rs827528, rs3808553 and rs12549394) in FZD6 gene were analyzed by polymerase chain reaction (PCR) and sequencing methods in 135 NTD patients and 135 normal controls. The allele, genotype and haplotype frequencies were calculated and analyzed to examine the relationship between FZD3/FZD6 SNPs and NTDs. Both T allele and TT genotype frequencies of the FZD6 rs3808553 loci in the NTDs group were significantly higher than those in the controls, and children with T allele and TT genotype were associated with increased NTDs risk (OR = 1.575, 95 % CI 1.112-2.230, P = 0.010 and OR = 2.811, 95 % CI 1.325-5.967, P = 0.023, respectively). There were no differences among different genotypes or alleles in other three SNPs. Haplotypes A-G-C and A-T-C in FZD6 were found associated with NTDs in the case-control study (OR = 0.560, 95 % CI 0.378-0.830, P = 0.004 and OR = 1.670, 95 % CI 1.126-2.475, P = 0.011, respectively). The rs3808553 of FZD6 is obviously associated with NTDs in Han population of northern China. The TT genotype may increase risk for NTDs.

Association between methylenetetrahydrofolate reductase C677T polymorphism and epilepsy susceptibility: a meta-analysis.

PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been implicated as a potential risk factor for epilepsy. To date, many case-control studies have investigated the association between MTHFR C677T polymorphism and epilepsy susceptibility. However, those findings were inconsistent. The objective of this study is to evaluate the precise association between MTHFR C677T polymorphism and epilepsy. METHODS: An electronic search of PubMed, EMBASE for papers on the MTHFR C677T polymorphism and epilepsy susceptibility was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. RESULTS: Ten case-control studies containing 1713 cases and 1867 controls regarding MTHFR C677T polymorphism were selected. A significant association between the MTHFR C677T polymorphism and epilepsy susceptibility was revealed in this meta-analysis (for T vs. C: OR=1.19, 95% CI=1.08-1.32; for TT+CT vs. CC: OR=1.20, 95% CI=1.05-1.38; for TT vs. CC: OR=1.48, 95% CI=1.20-1.83; for TT vs. CT+CC: OR=1.35, 95% CI=1.12-1.64). In subgroup analysis by ethnicity, the results also indicated the association between the MTHFR C677T polymorphism and epilepsy susceptibility within the Asian populations (for T vs. C: OR=1.55, 95% CI=1.15-2.07; for TT+CT vs. CC: OR=1.67, 95% CI=1.08-2.59; for TT vs. CC: OR=2.33, 95% CI=1.30-4.20; for TT vs. CT+CC: OR=1.89, 95% CI=1.12-3.18). CONCLUSION: The results indicated that MTHFR C677T polymorphism was associated with an increased risk of epilepsy. However, further studies in various regions are needed to confirm the findings from this meta-analysis.

Methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and susceptibility to Parkinson's disease: a meta-analysis.

BACKGROUND: The association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and susceptibility to Parkinson's disease (PD) was controversial in previous studies. The present study was therefore designed to investigate a more reliable estimate. METHODS: 15 studies were identified by a search of PubMed, EBMBASE, PDGENE, Elsevier, Springer Link, CBM (Chinese Biomedical Database), CNKI (Chinese National Knowledge Infrastructure), VIP (Chinese), and Wanfang (Chinese) databases, up to April 2013. Odds ratios (ORs) with corresponding 95% confidence interval (CI) were calculated using fixed effects model or random effects model. The subgroup analyses were made on the ethnicity. RESULTS: MTHFR C677T polymorphism had a significant association with susceptibility to PD in all genetic models (for T vs. C: OR=1.24, 95% CI=1.11-1.38; for TT+CT vs. CC: OR=1.27, 95% CI=1.10-1.46; for TT vs. CC: OR=1.56, 95% CI=1.22-1.98; for TT vs. CT+CC: OR=1.43, 95% CI=1.14-1.79). Subgroup analyses by ethnicity revealed that the association between the MTHFR C677T polymorphism and PD existed in Caucasian population and Asian population. However, no association was detected between the MTHFR A1298C polymorphism and PD. CONCLUSIONS: Results from this meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of PD. The MTHFR A1298C polymorphism may not increase the susceptibility to PD. Further studies are required to confirm our findings.