Embryonic exposure to aluminum chloride blocks the onset of spermatogenesis through disturbing the dynamics of testicular tight junctions via upregulating Slc25a5 in offspring.

Studies have revealed neurotoxicity, hepatotoxicity, and developmental and reproductive toxicity in mice exposed to aluminum. However, relatively few studies have been conducted to clarify the mechanism underlying the impact of embryonic exposure to aluminum on the development of the male reproductive system in offspring. Pregnant mice were administered aluminum chloride (AlCl3) by gavage from day 12.5 of gestation until birth. Our findings demonstrated that embryonic exposure to AlCl3 disrupted testicular development and spermatogenesis by impairing testicular architecture, reducing sperm count, and upregulating the expression of tight junction (TJ) protein between Sertoli cells (SCs). Further in vitro studies revealed that treatment with AlCl3 stabilized TJ proteins Occludin and ZO-1 expression by inhibiting ERK signaling pathway activation, thereby upregulating Slc25a5 expression which induced ATP production leading to disruption of cytoskeletal protein homeostasis. Therefore, the study provided a new mechanistic insight into how AlCl3 exposure interfered with testicular development and spermatogenesis while suggesting that Slc25a5 might be a target affected by AlCl3 influencing cell metabolism.

Identification of common genetic polymorphisms associated with down-regulated gonadotropin levels in an exome-wide association study.

OBJECTIVE: To investigate whether common genetic polymorphisms are associated with gonadotropin levels after down-regulation with daily gonadotropin-releasing hormone agonist and whether the polymorphisms of candidate variants influence the ovarian response to exogenous gonadotropins. DESIGN: Genetic association study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Subjects enrolled in an exploratory exome-wide association study (n = 862), a replication exome-wide association study (n = 86), and a classifier validation study (n = 148) were recruited from September 2016 to October 2018, September 2019 to September 2020, and January 2021 to December 2021, respectively. The included patients were aged ≤40 years and had a basal follicle-stimulating hormone (FSH) ≤12 IU/L. INTERVENTIONS: All participants received a luteal phase down-regulation long protocol. Genome DNA was extracted from the peripheral blood leukocytes. For the exploratory and replication cohorts, exome sequencing was conducted on a HiSeq 2500 sequencing platform. The multiplex polymerase chain reaction amplification technique and next-generation sequencing also were performed in the exploratory and replication cohorts. For the samples of the validation cohort, Sanger sequencing was performed. MAIN OUTCOME MEASURES: The primary endpoint was the gonadotropin levels after down-regulation, and the secondary endpoints were hormone levels and follicle diameters during stimulation, the total dose of FSH, duration of FSH stimulation, number of oocytes retrieved, and clinical pregnancy rate. RESULTS: In the exploratory cohort, we identified that FSHB rs6169 (P=2.71 × 10-24) and its single-nucleotide polymorphisms in high linkage disequilibrium were associated with the down-regulated FSH level. The same locus was confirmed in the replication cohort. Women carrying the C allele of FSHB rs6169 exhibited higher average estradiol level during stimulation (P=6.82 × 10-5), shorter duration of stimulation, and less amount of exogenous FSH (Pduration=0.0002; Pdose=0.0024). In the independent validation set, adding rs6169 genotypes into the prediction model for FSH level after down-regulation enhanced the area under the curve from 0.560 to 0.712 in a logistic regression model, and increased prediction accuracy by 41.05% when a support vector machine classifier was applied. CONCLUSION: The C allele of FSHB rs6169 is a susceptibility site for the relatively high level of FSH after down-regulation, which may be associated with increased ovarian FSH sensitivity.

A Rare B-Myeloid Conversion of Follicular Lymphoma into Clonally Related Acute Myeloid Leukemia: A Case Report.

Follicular lymphoma (FL) is a highly prevalent indolent lymphoma, and the risk of histological transformation is approximately 2-3% per year. Transformation of FL generally occurs in the same lineage (B cell lineage). Another rare form of disease progression is the transformation of neoplastic B-cells to another cell lineage such as acute myeloid leukemia (AML). The low incidence of B-myeloid transformation associated with poor prognosis hinders the establishment of model systems to identify molecular mechanisms. A 64-year-old woman was diagnosed with FL and achieved a satisfactory response after six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Approximately one month after treatment terminated, the disease progressed to AML with an increased white blood cell count and abnormal coagulation. Interestingly, nucleotide sequence analysis of the genomic region encoding the immunoglobulin heavy-chain variable domain showed the possibility of homologous transformation from lymphoma to leukemia cells. Although the patient experienced transient improvement after undergoing treatment with one cycle of idarubicin and cytarabine combined with etoposide, she relapsed and died 8 days after venetoclax salvage therapy. Patient with B-myeloid transformation was associated with an aggressive clinical course and poor prognosis. Conventional strategies for treating histologically transformed AML were ineffective. However, treatment with a Bcl-2 inhibitor could serve as an option. Here we review the literature relevant to this rare histological transformation of FL.

Proteome-centric cross-omics characterization and integrated network analyses of triple-negative breast cancer.

We report a comprehensive proteomic study of a 90-case cohort of paired samples of triple-negative breast cancer (TNBC) in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1-4) are stratified on the basis of global proteome and phosphoproteome, each of which exhibits distinct molecular and pathway features. Scaffold and co-expression network analyses of three proteomic datasets, integrated with those from genome and transcriptome of the same cohort, reveal key pathways and master regulators that, characteristic of TNBC subtypes, play important regulatory roles within and between scaffold sub-structures and co-expression communities. We find that NAE1 is a potential drug target for subtype iP-1, and a series of key molecules in fatty acid metabolism, such as AKT1/FASN, are plausible targets for subtype iP-2. Libraries of proteins, pathways and networks of TNBC provide a valuable molecular infrastructure for further clinical exploration and in-depth studies of the molecular mechanisms of the disease.

Promising Response to Lenalidomide-Combination Therapy in a Discordant Lymphoma Consisting of EBV-Positive Diffuse Large B-Cell Lymphoma and Angioimmunoblastic T-Cell Lymphoma: A Case Report.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) complicated with angioimmunoblastic T-cell lymphoma (AITL) is extremely rare and typically shows an aggressive clinical course and unsatisfactory prognosis. Here, we describe the case of a 77-year-old man who was referred to the hospital because of repeated fever, night sweats, and weight loss. He was finally diagnosed with a discordant lymphoma consisting of AITL and DLBCL, with significantly different maximum standardized uptake values on positron emission tomography/computed tomography. Based on his complex illness and poor performance status, the patient received six cycles of lenalidomide combined with R-miniCHOP regimen and achieved complete remission with tolerable and controlled toxicity. He subsequently received lenalidomide maintenance therapy and achieved sustained remission. We consider the possible causes of this discordance involved AITL and EBV-positive DLBCL, and the possible mechanism of lenalidomide action in both T-cell and B-cell non-Hodgkin lymphomas. Lenalidomide-combination therapy may be a preferable choice in patients with an EBV-associated discordant lymphoma.

Comprehensive Identification of Potential Crucial Genes and miRNA-mRNA Regulatory Networks in Papillary Thyroid Cancer.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy, with a recent global increase of 20% in age-related incidence. Ultrasonography and ultrasonography-guided fine-needle aspiration biopsy (FNAB) are the most widely used diagnostic tests for thyroid nodules; however, it is estimated that up to 25% of thyroid biopsies are cytologically inconclusive. Molecular markers can help guide patient-oriented and targeted treatment of thyroid nodules and thyroid cancer. METHODS: Datasets related to papillary thyroid cancer (PTC) or thyroid carcinoma (GSE129562, GSE3678, GSE54958, GSE138042, and GSE124653) were downloaded from the GEO database and analysed using the Limma package of R software. For functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology were applied to differentially expressed genes (DEGs) using the Metascape website. A protein-protein interaction (PPI) network was built from the STRING database. Gene expression, protein expression, immunohistochemistry, and potential functional gene survival were analysed using the GEPIA website, the Human Protein Atlas website, and the UALCAN website. Potential target miRNAs were predicted using the miRDB and Starbase datasets. RESULTS: We found 219 upregulated and 310 downregulated DEGs, with a cut-off of p < 0.01 and ∣log FC | >1.5. The DEGs in papillary thyroid cancer were mainly enriched in extracellular structural organisation. At the intersection of the PPI network and Metascape MCODEs, the hub genes in common were identified as FN1, APOE, CLU, and SDC2. In the targeted regulation network of miRNA-mRNA, the hsa-miR-424-5p was found to synchronously modulate two hub genes. Survival analysis showed that patients with high expression of CLU and APOE had better prognosis. CONCLUSIONS: CLU and APOE are involved in the molecular mechanism of papillary thyroid cancer. The hsa-miR-424-5p might have the potential to reverse the processes of papillary thyroid cancer by modulating the hub genes. These are potential targets for the treatment of patients with papillary thyroid cancer.

Recurrent giant cell tumour of the thoracic spine managed by total en bloc spondylectomy and denosumab therapy: a case report.

BACKGROUND: Giant cell tumour (GCT) of the bone is a rare, invasive benign bone tumour, which typically originates in the metaphyseal ends of long bones and rarely in the spine. Here, we report a rare case of recurrent GCT of the thoracic vertebra, which was managed by three-level total en bloc spondylectomy (TES) after denosumab therapy. CASE PRESENTATION: A 50-year-old woman presented with a 2-month history of progressive lower back pain. Magnetic resonance imaging revealed destruction of the T11 vertebra and a soft tissue mass. The patient underwent tumour resection. Computed tomography at the 2-year follow-up revealed relapse of the resected tumour, which had spread to the T12 vertebral body. Subsequently, denosumab therapy was administered to the patient for 1 year. The growth of the tumour was controlled, and its boundary line was clear. Thereafter, TES for the T10-T12 vertebrae was performed, and spinal reconstruction was completed through a one-stage single posterior approach. The patient's condition improved postoperatively, and no evidence of recurrence of GCT of the bone or spinal deformity was observed at the 32-month follow-up. CONCLUSIONS: Denosumab therapy contributed to tumour regression. Three-level TES may be an effective and feasible strategy for managing large recurrent GCTs of the spine after denosumab therapy.

Atorvastatin ameliorates depressive behaviors and neuroinflammatory in streptozotocin-induced diabetic mice.

Depression is a chronic and progressive syndrome and commonly associated with several neuropsychiatric comorbidities, of which depression is the most studied. It has been demonstrated that statins also have anti-inflammatory and immunomodulatory properties, which being explored for potential benefits in depression. However, the role of statins in the treatment of diabetes-related depression has not been well examined. Herein, we investigated the effects of atorvastatin on depressive behaviors and neuroinflammation in streptozotocin-induced diabetic mice. Our data indicated that oral administration of atorvastatin at 10 or 20 mg/kg for 3 weeks markedly ameliorated diabetes-associated depressive behaviors reflected by better performance in sucrose preference test (SPT), tail suspension test (TST), and novelty-suppressed feeding test (NSFT). The study further showed that atrovastatin decreased the expression of nucleus NF-κB p65 expression and ameliorated neuroinflammatory responses in prefrontal cortex as evidenced by less Iba-1-positive cells and lower inflammatory mediators including IL-1ß and TNF-α. As expected, atorvastatin-treated diabetic mice exhibited significant improvement of hyperlipidemia rather than hyperglycemia. These results suggest that atorvastatin has the potential to be employed as a therapy for diabetes-related depression.

Serial plasma DNA levels as predictors of outcome in patients with acute traumatic cervical spinal cord injury.

BACKGROUND: Acute traumatic cervical spinal cord injury (SCI) is a leading cause of disability in adolescents and young adults worldwide. Evidence from previous studies suggests that circulating cell-free DNA is associated with severity following acute injury. The present study determined whether plasma DNA levels in acute cervical SCI are predictive of outcome. METHODS: In present study, serial plasma nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) levels were obtained from 44 patients with acute traumatic cervical SCI at five time points from day 1 to day 180 post-injury. Control blood samples were obtained from 66 volunteers. RESULTS: Data showed a significant increase in plasma nDNA and mtDNA concentrations at admission in SCI patients compared to the control group. Plasma nDNA levels at admission, but not plasma mtDNA levels, were significantly associated with the Japanese Orthopaedic Association (JOA) score and Injury Severity Score in patients with acute traumatic cervical SCI. In patients with non-excellent outcomes, plasma nDNA increased significantly at days 1, 14 and 30 post-injury. Furthermore, its level at day 14 was independently associated with outcome. Higher plasma nDNA levels at the chosen cutoff point (> 45.6 ng/ml) predicted poorer outcome with a sensitivity of 78.9% and a specificity of 78.4%. CONCLUSIONS: These results indicate JOA score performance and plasma nDNA levels reflect the severity of spinal cord injury. Therefore, the plasma nDNA assays can be considered as potential neuropathological markers in patients with acute traumatic cervical SCI.

Magneto-Coulomb Drag and Hall Drag in Double-Layer Dirac Systems.

We develop a theory of Coulomb drag due to momentum transfer between graphene layers in a strong magnetic field. The theory is intended to apply in systems with disorder that is weak compared to Landau level separation, so that Landau level mixing is weak but strong compared to correlation energies within a single Landau level, so that fractional quantum Hall physics is not relevant. We find that, in contrast to the zero-field limit, the longitudinal magneto-Coulomb drag is finite and, in fact, attains a maximum at the simultaneous charge neutrality point (CNP) of both layers. Our theory also predicts a sizable Hall drag resistivity at densities away from the CNP.

Safety and Immunogenicity of a Nonadjuvant Human Papillomavirus Type 6 Virus-like Particle Vaccine in Recurrent Respiratory Papillomatosis.

OBJECTIVES: To assess the safety and immunogenicity of a nonadjuvant human papillomavirus (HPV) type 6 L1 virus-like particle (VLP) vaccine in recurrent respiratory papillomatosis (RRP) in local Chinese patients. METHODS: Patients with RRP who had undergone surgical treatment before intramuscular administration of an escalating dose of HPV type 6 L1 VLPs (1, 5, and 25 µg at 4 weekly intervals) as part of their treatment were followed up for more than 10 years. Efficacy was assessed by detecting the vaccine-induced type-specific antibody titer, calculating the intersurgical interval, and observing recurrence or remission of papillomas after receiving the vaccine. RESULTS: Nonadjuvant HPV vaccine was generally well tolerated, with no serious vaccine-related adverse episodes. It induced seroconversion for each vaccine-related HPV type. At week 12 (4 weeks after injecting 25 µg), the vaccine-induced type-specific antibody titer was significantly high. Analysis of all patients found a significant increase in the intersurgical interval and decrease in the scores. One patient (16.7%; female) experienced complete remission. Five patients (83.3%) (two males and three females) experienced partial remission. In total, complete or partial remission was achieved in six (100%) patients. CONCLUSIONS: Administration of nonadjuvant HPV type 6 L1 VLPs vaccine to RRP was generally well tolerated and highly immunogenic.

Anti-CCP-positive patients with RA have a higher 10-year probability of fracture evaluated by FRAX®: a registry study of RA with osteoporosis/fracture.

BACKGROUND: Positive anticyclic citrullinated peptide (anti-CCP+) is associated with bone loss in patients with rheumatoid arthritis (RA). However, whether overall positivity or specific levels of anti-CCP are associated with prevalent fracture or a 10-year probability of fracture remains unclear. METHODS: This interim analysis of an RA registry was conducted at Chang Gung Memorial Hospital in Kaohsiung (CGMHK) for RA-related osteoporosis/fracture. Consecutive patients with RA who had visited the rheumatology clinic at CGMHK since September 1, 2014, and fulfilled the classification criteria of RA were enrolled. The demographics, disease duration, Disease activity in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR), lifestyle, evidence of previous fracture, risk factors of fracture in the Fracture Risk Assessment Tool (FRAX®), and FRAX® score of each participant were collected. Anti-CCP, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and bone mineral density (BMD) were measured at enrollment. The patients were grouped by positivity or quartiles of anti-CCP level (I-IV). RESULTS: Five hundred twenty-one patients with RA were enrolled through May 31, 2016. In total, 359 (68.9%) patients were anti-CCP+. Compared with anti-CCP- patients, anti-CCP+ patients had a significantly higher DAS28-ESR (p = 0.0001) and 10-year probability of major (15.0 [18.9] vs. 12.0 [15.3], p = 0.0461) or hip (5.0 [9.2] vs. 3.6 [8.2], p = 0.0118) fracture, but a significantly lower BMD of the FN (p = 0.0196). The rates of osteoporosis and previous fracture were comparable. There were 130, 127, 132, and 132 patients in groups I-IV, respectively. The DAS28-ESR was significantly different (p = 0.0001) among the groups and correlated to anti-CCP levels. The BMD and 10-year probability of major (p = 0.0067) and hip (p = 0.0013) fracture among the groups were also different. CONCLUSIONS: Anti-CCP+ RA patients had a higher 10-year probability of major or hip fracture, independent of anti-CCP levels, and a lower BMD of the FN than anti-CCP- patients.

Effect of the initiation of progesterone supplementation in in vitro fertilization-embryo transfer outcomes: a prospective randomized controlled trial.

OBJECTIVE: To analyze the influence of the start point of luteal support on clinical pregnancy rate, implantation rate, and live birth rate of in vitro fertilization and embryo transfer (IVF-ET) cycles. DESIGN: Single-center prospective randomized controlled trial. SETTING: University-affiliated IVF unit. PATIENT(S): Women ≤35 years of age with day 3 FSH levels <15 mIU/mL, who were undergoing their first IVF-ET cycles and received ovarian stimulation with the use of a GnRH agonist long protocol. INTERVENTION(S): The patients were randomized on the day of hCG trigger to receive luteal phase support either 1 day after oocyte retrieval (group A) or on the day of oocyte retrieval (group B). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, implantation rate, miscarriage rate in the first trimester of pregnancy, and live birth rate per embryo transfer cycle. RESULT(S): Two hundred thirty-three patients were enrolled in this study: 117 were assigned to group A and 116 to group B. The clinical pregnancy rate (group A vs. group B: 55.3% vs. 51.5%), implantation rate (38.4% vs. 38.0%), and miscarriage rate (7.7% vs. 7.5%) were similar between the two groups. The live birth rate also did not significantly differ between the two groups (45.7% vs. 46.6%). CONCLUSION(S): Our study indicated that the initiation of progesterone supplementation 1 day after oocyte retrieval did not decrease the clinical pregnancy rate, implantation rate, or live birth rate in women undergoing IVF-ET cycles with the use of the GnRH agonist long protocol. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IPR-14005293.

Delayed anti-TNF therapy increases the risk of total knee replacement in patients with severe rheumatoid arthritis.

BACKGROUND: This study evaluated the effect of early anti-tumor necrosis factor (TNF) therapy in patients with severe rheumatoid arthritis (RA) on the subsequent risk of total knee replacement (TKR) surgery. METHODS: This retrospective observational study included a hospital-based cohort of 200 patients diagnosed with severe RA who received treatment with anti-TNF therapy between 2003 and 2014. Clinical parameters including age, sex, body mass index, and the time from the diagnosis of RA to the initiation of anti-TNF therapy were analyzed. RESULTS: Of the 200 enrolled patients, 84 underwent an early intervention (≤3 years from the diagnosis of RA to the initiation of anti-TNF therapy), and 116 underwent a late intervention(>3 years from the diagnosis of RA to the initiation of anti-TNF therapy). Five (6.0%) patients in the early intervention group underwent TKR compared to 31 (26.7%) in the late intervention group (p = 0.023). After adjusting for confounding factors, the late intervention group still had a significantly higher risk of TKR (p = 0.004; odds ratio, 5.572; 95% confidence interval, 1.933-16.062). Those receiving treatment including methotrexate had a lower risk of TKR (p = 0.004; odds ratio, 0.287; 95% confidence interval, 0.122-0.672). CONCLUSIONS: Delayed initiation of anti-TNF therapy in the treatment of severe RA was associated with an increased risk of TKR surgery. Adding methotrexate treatment decreased the risk of future TKR.

Beyond bone mineral density, FRAX-based tailor-made intervention thresholds for therapeutic decision in subjects on glucocorticoid: A nationwide osteoporosis survey.

Glucocorticoid-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis and confers a substantial risk for future fractures. Several recent guidelines for GIOP management have recommended the use of intervention thresholds to direct pharmacological therapy in those at high risk of fracture. The aim of this study was to analyze the characteristics of subjects on a glucocorticoid (GC) and to implement the Fracture Risk Assessment Tool (FRAX)-based intervention threshold for therapeutic decision-making.This was a cohort substudy of a nationwide osteoporosis screening program conducted in Taiwan from 2008 to 2011. All participants were requested to complete a questionnaire including FRAX elements, and antiosteoporosis medication (AOM) history was assessed before bone mineral density (BMD) measurement. GC users were recruited as the study group. Controls comprised randomly selected age- and sex-matched non-GC users. Individual intervention threshold (IIT) was set at individual-specific FRAX probability of a major osteoporotic fracture, relative to subjects with prior fractures. The characteristics and calculated IIT of all participants were analyzed.A total of 8704 participants were enrolled, including GC users (n = 807) and controls (n = 7897). There was no significant difference in BMD between GC users and controls. Clinical fracture risks, including previous fracture, parental hip fracture, rheumatoid arthritis, and secondary osteoporosis were higher in GC users than in controls. GC users had a higher 10-year probability of either major or hip fracture than controls. The proportion of GC users with a 10-year probability of major osteoporotic fracture above IIT was higher than in controls (75.0% vs 10.6%; P < 0.001). Only 20.3% of GC users and 30.5% of controls whose fracture risk was above IIT reported taking AOM.These findings suggest that more GC users should receive active intervention based on IIT, regardless of BMD. However, less than one-fourth of GC users whose fracture risk was above IIT received AOM, indicating that GIOP is markedly undertreated. We recommend commencing AOM for GIOP according to IIT, instead of BMD alone.

Resolving defence mechanisms: A perspective based on dissipative structure theory.

Theories and classifications of defence mechanisms are not unified. This study addresses the psychological system as a dissipative structure which exchanges information with the external and internal world. When using defence mechanisms, the cognitive-affective schema of an individual could remain stable and ordered by excluding psychological entropy, obtaining psychological negentropy or by dissipating the energy of self-presentation. From this perspective, defences can be classified into three basic types: isolation, compensation and self-dissipation. However, not every kind of defence mechanisms can actually help the individual. Non-adaptive defences are just functioning as an effective strategy in the short run but can be a harmful approach in the long run, while adaptive defences could instead help the individual as a long-term mechanism. Thus, we would like to suggest that it is more useful for the individual to use more adaptive defence mechanisms and seek out social or interpersonal support when undergoing psychic difficulties. As this model of defences is theoretical at present, we therefore aim to support and enrich this viewpoint with empirical evidence.

Corrigendum to "The Value of Safflower Yellow Injection for the Treatment of Acute Cerebral Infarction: A Randomized Controlled Trial".

[This corrects the article DOI: 10.1155/2015/478793.].

Association between rs1801133 polymorphism and risk of adult ischemic stroke: Meta-analysis based on case-control studies.

BACKGROUND: This study is aimed to quantify the strength of the association between rs1801133 polymorphism and ischemic stroke risk. METHODS: We have searched Medline, Springer, and Embase for studies investigating the association between rs1801133 polymorphism and ischemic stroke risk. We estimated the pooled odds ratio with its 95% confidence intervals to assess this possible association. RESULTS: Forty case-control studies comprising 8809 cases and 9130 controls are eligible for this meta-analysis on the basis of relation of rs1801133 polymorphism to ischemic stroke risk. Hardy-Weinberg equilibrium was used to perform in controls for excluding articles. The overall analysis suggested that rs1801133 polymorphism was associated with increased risk of ischemic stroke (ORT versus C=1.16, 95% CI 1.10-1.22; ORTT versus TC+CC=1.32, 95% CI 1.18-1.47; ORTT+TC versus CC=1.11, 95% CI 1.04-1.18). Subgroup analysis showed that T allele was a significant strength between T allele and stroke risk in Asian, Caucasian, male and young-middle populations (OR=1.19, 1.11, 1.30, 1.16, respectively). Compared with TC+CC, TT genotype was found to be a risk factor for developing ischemic stroke in Asian, Caucasian and male (OR=1.41, 1.20, 1.77, respectively). Additionally, TT+TC retained a significant increase for ischemic stroke only in Asian comparable to CC genotype (OR=1.14). CONCLUSIONS: The rs1801133 polymorphism could be capable of increasing ischemic stroke susceptibility in Asian, male and young-middle populations.