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The dopamine and oxidative stress hypotheses are leading theories of the pathoetiology of schizophrenia (SCZ). Glutathione Peroxidase 1 (GPx-1), a major antioxidant enzyme, and the most abundantly expressed member of the GPx family, plays an important role in metabolic dopamine changes, which are closely related to neurological and psychiatric disorders. The impact of GPx-1 polymorphisms has rarely been explored in the field of SCZ. Here, we explored the possible relationship between GPx-1 gene polymorphisms and SCZ in Chinese Han subjects by using the polymerase chain reaction-restriction fragment length polymorphism method. DNA from 786 patients (360 patients with schizophrenia and 426 healthy controls) was genotyped for the single-nucleotide polymorphisms rs1800668 C/T and rs1050450 C/T in GPx-1 using polymerase chain reaction-restriction fragment length polymorphism analysis. Analysis of the association between GPx-1 and SCZ was performed using SPSS 22.0, while Haploview 4.2 software and SHEsis software were used to perform linkage disequilibrium analysis and haplotype analysis. The results indicated that the GPx-1 polymorphisms rs1050450 and rs1800668 were associated with SCZ. We found that the C-allele of rs1800668 C/T may be a protection factor against SCZ in general, but in particular, for males. Furthermore, the CT and TC (GPx-1 rs1800668 C/T and rs1050450 C/T) haplotypes may be susceptible to SCZ in the population. Finally, no significant differences in allelic or genotypic frequencies of rs1050450 were detected between cases and controls from whole or stratification analyses by gender. GPx-1 polymorphisms are related to SCZ in Chinese Han subjects. Our results suggested that GPx-1 may be a potential gene that influences SCZ.

Two common polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012 (approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group (P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke (OR = 1.844, 95% CI: 1.286-2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke (OR = 1.366, 95% CI: 1.077-1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype (OR = 2.953, 95% CI: 2.082-4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction (OR = 3.404, 95% CI: 1.631-7.102, P < 0.001) and additive interaction (RERI = 41.705, 95% CI: 14.586-68.824, AP = 0.860; 95% CI: 0.779-0.940; S = 8.170, 95% CI: 3.772-17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele (OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele (OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.

The G-protein-coupled purinergic receptor P2Y2 (P2RY2) plays an important role in the mechanism of atherosclerosis, which is relevant to ischemic stroke. This retrospective case-control study aimed to assess the relationship between P2RY2 gene polymorphisms and ischemic stroke risk in the northern Han Chinese population. In this study, clinical data and peripheral blood specimens were collected from 378 ischemic stroke patients and 344 controls. The ischemic stroke participants were recruited from the First Affiliated Hospital of China Medical University and the First Affiliated Hospital of Liaoning Medical University. The controls were recruited from the Health Check Center at the First Affiliated Hospital of China Medical University. Ischemic stroke patients were divided into two subgroups according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification: large-artery atherosclerosis (n = 178) and small-artery occlusion (n = 200) strokes. All subjects were genotyped for three single nucleotide polymorphisms (rs4944831, rs1783596, and rs4944832) in the P2RY2 gene using peripheral venous blood samples. The distribution of the dominant rs4944832 phenotype (GG vs. GA+AA) differed significantly between small-artery occlusion patients and control subjects (odds ratio (OR) = 1.720, 95% confidence interval (CI): 1.203-2.458, P < 0.01). Multivariable logistic regression analysis revealed that the GG genotype of rs4944832 was significantly more prevalent in small-artery occlusion patients than in control subjects (OR = 1.807, 95% CI: 1.215-2.687, P < 0.01). The overall distribution of the haplotype established by rs4944831-rs1783596-rs4944832 was significantly different between ischemic stroke patients and controls (P < 0.01). In ischemic stroke patients, the frequency of the G-C-G haplotype was significantly higher than in control subjects (P = 0.028), whereas the frequency of the T-C-A haplotype was lower than in control subjects (P = 0.047). These results indicate that the G-C-G haplotype of P2RY2 is a susceptibility haplotype for ischemic stroke. In addition, the GG genotype of rs4944832 may be associated with the development of small-artery occlusion in the northern Han Chinese population. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of China Medical University on February 20, 2012 (No. 2012-38-1) and the First Affiliated Hospital of Liaoning Medical University, China, on March 1, 2013 (No. 2013-03-1). All participants gave their informed consent. This trial was registered with the ISRCTN Registry (ISRCTN11439124) on October 24, 2018. Protocol version (1.0).

Background： Neuromyelitis optica （NMO） and multiple sclerosis （MS） are autoimmune demyelinating diseases of the central nerve system, lnterleukin-7 （IL-7） and interleukin-7 receptor alpha （IL-7Rα） were proved to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes. The variants of both genes had been identified to be associated with MS susceptibility in Caucasian, Japanese and Korean populations. However, the association of these variants with NMO and MS has not been well studied in Chinese Southeastern Han population. Here, we aimed to evaluate the association of six IL-7 variants （rsl520333, rs1545298, rs4739140, rs6993386, rs7816065, and rs2887502） and one variant of IL-7RA （rs6897932） with NMO and MS among Chinese Han population in southeastern China. Methods： Matrix-assisted laser desorption/ionization time of flight mass spectrometry （MassARRAY system） and Sanger sequencing were used to determine the variants of IL-7 and IL-7RA in 167 NMO patients, 159 MS patients and 479 healthy controls among Chinese Han population in southeastern China. Samples were excluded if the genotyping success rate 〈90%. Results： Statistical differences were observed in the genotypes of IL-7 rs1520333 in MS patients and IL-7RA rs6897932 in NMO patients, compared with healthy controls （P = 0.035 and 0.034, respectively）. There was a statistically significant difference in the genotypes of IL-7 rs2887502 between MS and NMO patients （P = 0.014）. And there were statistically significant differences in the rs6897932 genotypes （P = 0.004） and alleles （P = 0.042） between NMO-IgG positive patients and healthy controls. Conclusions： The study suggested that among Chinese Hart population in southeastern China, the variant of IL-7RA （rs6897932） was associated with NMO especially NMO-IgG positive patients while the variant of IL-7 （rs1520333） with MS patients. And the genotypic differences of IL-7 rs2887502 between MS and NMO indicated the different genetic backgrounds of these two diseases.

Background： A study has identified several novel susceptibility variants of the mitogen-activated protein kinase kinase kinase kinase 4 （MAP4K4） gene for type 2 diabetes mellitus （T2DM） within the German population. Among the variants, five single nucleotide polymorphisms （SNPs） of MAP4K4 （rs1003376, rs1 1674694, rs2236935, rs2236936, and rs6543087） showed significant association with T2DM or diabetes-related quantitative traits. We aimed to evaluate whether common SNPs in the MAP4K4 gene were associated with T2DM in the Chinese population. Methods： Five candidate SNPs were genotyped in 996 patients newly diagnosed with T2DM and in 976 control subjects, using the SNPscanTM method. All subjects were recruited from the Second Affiliated Hospital, Harbin Medical University from October 2010 to September 2013. We evaluated the T2DM risk conferred by individual SNPs and haplotypes using logistic analysis, and the association between the five SNPs and metabolic traits in the subgroups. Results： Of the five variants, SNP rs2236935T/C was significantly associated with T2DM in this study population （odds ratio = 1.293; 95% confidence interval： 1.034-1.619, P= 0.025）. In addition, among the controls, rs1003376 was significantly associated with an increased body mass index （P = 0.045） and homeostatic model assessment-insulin resistance （P = 0.037）. Conclusions： MAP4K4 gene is associated with T2DM in a Chinese Han population, and MAP4K4 gene variants may contribute to the risk toward the development of T2DM.

To develop a population pharmacokinetic (PK) model of tacrolimus in Chinese Han renal transplant population and establish the influence of different covariates (especially different / / genotype) on PK properties. Trough tacrolimus concentrations, clinical characteristics and genotypes were collected from 141 adult renal transplant recipients after transplantation. The population PK analysis was carried out using the nonlinear mixed-effect modeling software NONMEM version 3.4.2. Tacrolimus PK profiles exhibited high interpatient variability. A two compartment model with first-order input and elimination described the tacrolimus PK profiles in the studied population. Among the genotypes, only genotype was confirmed to have clinical significance. Our final model confirmed that plays a more significant role in tacrolimus PK and could affect the blood concentrations and CL/F (clearance rate/bioavailbility). This model is expected to help to improve individualized tacrolimus dosing.

To systematically investigate the genetic polymorphisms of the CYP3A4 gene in a Han Chinese population. The promoter and exons of CYP3A4 gene in 1114 unrelated, healthy Han Chinese subjects were amplified and genotyped by direct sequencing. In total, five previously reported alleles (*1G, *4, *5, *18B and *23) were detected, of which one allele (*23) was reported for the first time in Han Chinese population. Additionally, seven novel exonic variants were also identified and designated as new alleles CYP3A4*28-*34. This study provides the most comprehensive data of CYP3A4 polymorphisms in Han Chinese population and detects the largest number of novel CYP3A4 alleles in one ethnic group.

Objectives The NR5A2 and RYR2 genes are important players in steroid metabolism and play an important role in cancer research. In this research, we want to evaluate the effect of NR5A2 and RYR2 polymorphisms on breast cancer (BC). Methods Four single nucleotide polymorphisms on NR5A2 and RYR2 were selected to genotype by Agena MassARRAY in 379 BC patients and 407 healthy controls. Using the PLINK software to calculate the Odds ratio (OR) and 95% confidence intervals (CIs) via the logistic regression analysis to evaluate the risk for BC. Results We found that NR5A2 rs2246209 significantly decreased the risk of BC with the AA genotype (OR 0.58, 95%CI 0.34–0.99, p  = 0.049), and recessive model (OR 0.59, 95%CI 0.35–0.99, p  = 0.046); rs12594 in the RYR2 gene significantly decreased the risk of BC in the GG genotype (OR 0.44, 95%CI 0.22–0.88, p  = 0.020), and recessive model (OR 0.43, 95%CI 0.21–0.85, p  = 0.016). Further stratification analysis showed that NR5A2 rs2246209 was related to a lower incidence of BC affected by age, lymph nodes metastasis, and tumor stage; RYR2 rs12594 was related to a decreased BC risk restricted by age, estrogen receptor (ER), progesterone receptor (PR), menopausal status, tumor size, and tumor stage. Rs12594 in the RyR2 gene remained significant on the genetic susceptibility of PR-positive BC after Bonferroni correction ( p  < 0.0125). Conclusions This study provides an evidence that NR5A2 rs2246209 and RYR2 rs12594 decreased the risk of breast cancer.

To evaluate the correlation between plasma fibrinogen levels and acute myocardial infarction (AMI) in the Chinese Han population. A total of 1522 patients with incident AMI and 6125 controls were recruited between January 1, 2010, and December 31, 2013. The relationship between fibrinogen levels and incident AMI was evaluated using multivariable-adjusted logistic regression, and the possible interaction effects between fibrinogen and other risk factors on incident AMI were investigated. When modeled as a continuous variable, a 1 g/L increase in fibrinogen level was associated with a 91% increase in the risk of AMI [odds ratio (OR):1.91; 95% confidence interval (CI):1.63–2.23 in women, 1.86:1.70–2.03 in men, and 1.85:1.72–2.00 in total]. Compared to 1st quartile of fibrinogen levels, the adjusted ORs for first incident AMI was 3.25 (2.67–3.96) for the fourth quartile, 1.61 (1.30–1.99) for the third one, 1.18 (0.96–1.46) for the second one ( P  < 0.001). High fibrinogen levels are associated with an increased risk of incident AMI in the Chinese Han population, and fibrinogen could be an important biomarker for AMI risk assessment.

ObjectiveSystemic sclerosis (SSc) is a heterogeneous connective tissue disease that is commonly subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) based on the extent of skin involvement. This subclassification may not reflect the full range of clinical phenotypic variation. This study aimed to investigate clinical features and aggregation of patients with SSc in Chinese based on SSc manifestations and organ involvements, in order to achieve precise treatment of SSc early prevention of complications.MethodsIn total 287 SSc patients were included in this study. A cluster analysis was applied according to 13 clinical and serologic variables to determine subgroups of patients. Survival rates between obtained clusters and risk factors affecting prognosis were also compared.ResultIn this study, six clusters were observed: cluster 1 (n = 66) represented the skin type, with all patients showing skin thickening. In cluster 2 (n = 56), most patients had vascular and articular involvement. Cluster 3 (n = 14) individuals mostly had cardiac and pulmonary involvement. In cluster 4 (n = 52), the gastrointestinal type, 50 patients presented with stomach symptoms and 28 patients presented with esophageal symptoms. In cluster 5 (n = 50), patients barely had any major organ involvement. Cluster 6 (n = 49) included 46% of all patients presenting with renal crisis.ConclusionThe results of our cluster analysis study implied that limiting SSc patient subgroups to those based only on skin involvement might not capture the full heterogeneity of the disease. Organ damage and antibody profiles should be considered when identifying homogeneous patient groups with a specific prognosis.Key Points• Provides a new method of categorizing SSc patients.• Can better explain disease progression and guide subsequent treatment.