Genomic Landscape of RTK/RAS Pathway and Tumor Immune Infiltration as Prognostic Indicator of Lung Adenocarcinoma.

The RTK/RAS pathway is an oncogenic signaling pathway for which many targeted drugs have been developed; however, survival remains poor. A combination of targeted therapy and immunotherapy has emerged as an option for improving cancer treatment responses. In this study, on the basis of the expression, survival, single nucleotide variation (SNV), copy number variation (CNV), and methylation data of lung adenocarcinoma (LUAD) from The Cancer Genome Atlas database, we comprehensively analyzed the genomic changes in the RTK/RAS pathway and their associations with tumor-infiltrating lymphocytes (TIL) and prognosis in LUAD to provide the genomics landscape of RTK/RAS with TIL and prognosis. We found that two rarely mutated genes, mitogen-activated protein kinase kinase 1 and insulin-like growth factor 1 receptor, were significantly associated with the worse survival of patients with LUAD. Patients with LUAD and co-mutation of KRAS proto-oncogene (KRAS) and neurofibromin 1 genes had worse survival, and the underlying mechanism could be insufficient for protein synthesis and intracellular signal deactivation. Methylation of the Rac family small GTPase 1 (RAC1) was associated with better survival. The SNVs of the top mutated genes, including epidermal growth factor receptor (12.7%), neurotrophic receptor tyrosine kinase 3 (7.8%), erb-b2 receptor tyrosine kinase 4 (8.5%), and KRAS (29.6%), were associated with T cell exhaustion in LUAD. To construct nomograms, we further screened the genes whose genomic changes were closely associated with survival and immune infiltration. The nomograms performed well in predicting disease-specific survival (DSS) with a concordance index of 0.7 (0.589, 0.811) and overall survival with a concordance index of 0.689 (0.603, 0.775) in test set; they also showed good correspondence between actual and ideal nomogram predictions. Tumor stage, RAC1 methylation, and type 1 regulatory T cells greatly contributed to DSS and OS nomograms. In summary, we provided a comprehensive genomic profile of the RTK/RAS pathway in LUAD and its association with immune cell infiltration and prognosis of LUAD. This profile would serve as a basis for developing better therapeutic strategies, improving patient prognosis, and understanding the mechanisms of immune disturbance from the perspective of oncogenic pathways of LUAD.

[Transcriptome analysis in fetal lungs of SRC1/SRC2 double-knockout mice].

Steroid receptor coactivators (SRCs) significantly increase the transcriptional activity of various steroid hormone receptors, and play an important regulatory role in a variety of physiological functions such as food intake, sleep, stress response and reproduction. Previous studies have found that pregnant mice carrying fetuses with SRC1/2 double-knockout (dKO) manifested delayed labor, partly due to the hypoplasia of fetal lungs and the decreased secretion of pulmonary surfactant protein-A (SP-A) and platelet activating factor (PAF). However, there is still a lack of systematic analysis of the changes in gene expression at the whole transcriptome level in the fetal lungs of SRC1/2 dKO mice. In this study, the SRC1KO, SRC2KO, SRC1/2 dKO and wild-type (WT) mouse fetal lung samples were collected at 18.5 days post coitus. The Illumina platform was employed for transcriptome mRNA sequencing, and then the differentially expressed genes (DEGs) were annotated and analyzed by GO and KEGG analysis. The results showed that the proportion of quality score of the sequencing data above Q30 in all samples was more than 92% and passed the quality control. Compared with WT fetal lungs, SRC1KO and SRC2KO fetal lungs had 61 and 32 DEGs, respectively; SRC1/2 dKO fetal lungs had 480, 11 and 901 DEGs compared with WT, SRC1KO and SRC2KO fetal lungs, respectively. Among these genes, Aspg, Crispld2, Eln, Ntsr2, Slc10a6 and Vgll3 were the unique DEGs of SRC1/2 dKO fetal lungs compared with other genotype mice. Real-time PCR and Western blotting verified the reliability of transcriptome sequencing results. The GO analysis of the DEGs between SRC1/2 dKO and WT mouse fetal lungs showed that the DEGs were significantly enriched in the extracellular space, extracellular region, and extracellular matrix in terms of cellular component. In the biological process, they were significantly enriched in the term of development of multiple organs. KEGG pathway analysis showed that the DEGs were mainly enriched in signaling pathways such as the complement system, extracellular matrix-receptor interactions, and protein digestion and absorption. In summary, this study comprehensively revealed the changes of gene expression in the fetal lungs of SRC1/2 dKO mice at the transcriptome level, which provides a new theoretical basis for the study of the developmental regulatory mechanism of the fetal lung during pregnancy, and the fetus-derived signals that affect the initiation of labor.

Differential Survival Outcomes Between De Novo and Secondary Acute Promyelocytic Leukemia: An Updated Population-based study.

BACKGROUND: Whether the characteristics and outcome of secondary acute promyelocytic leukemia (s-APL) are similar to de no APL (dn-APL) remains unknown. PATIENTS AND METHODS: Using the SEER database, we identified 3877 patients with APL diagnosed from 2000 to 2014, including 465 s-APL and 3412 dn-APL. RESULTS: Compared with dn-APL, s-APL werecharacterized by older median age, and a higher early mortality rate. Multivariate Cox model showed s-APL, older age, earlier year of diagnosis, and male gender were independently associated with worse survival. Notably, s-APL had a significantly inferior survival regardless of gender, race, marital status, and year of diagnosis. However, the difference between the 2 cohorts was only evident in younger patients (≤ 65 years) but was lost in older patients (> 65 years). Additionally, the majority of index cancer type was breast and prostate in female and male s-APL, respectively. Latency < 3 years was associated with superior survival in s-APL with breast index cancer. CONCLUSIONS: Inferior survival of s-APL points to the need for treatment improvement.

Cytotoxic and Anti-Inflammatory Sesquiterpenes from the Whole Plants of Centipeda minima.

Sixteen new sesquiterpene lactones (1-16) along with 13 known analogues (17-29) were isolated from the whole plants of Centipeda minima. The structures of 1-16 were delineated by the combination of NMR spectroscopic experiments, HRESIMS, single-crystal X-ray diffraction analyses, and ECD spectra. Compounds 23-26 showed potent cytotoxicity against Hela, HCT-116, and HepG2 cells with IC50 values of 0.8-2.6, 0.4-3.3, and 1.1-2.6 µM, respectively. Compounds 8, 15, and 24 exhibited significant inhibitory activity on the production of nitric oxide in the lipopolysaccharide-activated RAW 264.7 mouse macrophage cell line, with IC50 values ranging from 0.1 to 0.2 µM.

Posterior reversible encephalopathy syndrome induced by food poisoning in a pediatric patient: a case report.

Posterior reversible encephalopathy syndrome (PRES) can develop in patients following exposure to multiple triggers, including blood pressure fluctuations, kidney diseases, immunosuppressive agents, chemotherapy, or autoimmune disorders. However, to the best of our knowledge, the development of PRES secondary to food poisoning has not been previously reported, especially in a pediatric patient. Here, we report a 13-year-old boy who presented with PRES following the consumption of palmatum (a chicken feet dish). The patient presented with headache, vomiting, and altered consciousness. Neuroimaging findings revealed white matter hyperintensities in a bilateral, symmetrical, and parieto-occipital pattern. The patient was diagnosed with PRES and was managed with fluid expansion and a short-term mannitol regimen (1 g/kg every 12 hours for 3 days). Neuroimaging findings returned to normal at 8 days after admission. Food poisoning may therefore be a new possible trigger for PRES. A timely PRES diagnosis is recommended to prevent possible central nervous system complications.

Prevalence of Oral Mucosal Diseases in Older Adults in Mainland China: A Meta-Analysis of Observational Studies.

Oral mucosal disease (OMD) is a public health challenge globally, but the epidemiological findings in older adults have been inconsistent in China. Thus, this meta-analysis was carried out to explore the prevalence of OMD and its moderating factors in this population. An electronic literature search was conducted of both international (PubMed, PsycINFO, and EMBASE) and Chinese (China National Knowledge Infrastructure and WanFang) databases from inception to November 1, 2019. The Der-Simonian and Laird random effects model was used to synthesize the prevalence of OMD and its 95% confidence intervals (95% CI). Twenty-four studies covering 23,653 older adults were included. The pooled prevalence of OMD was 23% (95% confidence interval: 17.9%-29.0%) Subgroup analyses and meta-analysis revealed that the prevalence of OMD was significantly associated with the reporting sampling, year of publication, and survey (all p values <0.05). This meta-analysis found that the prevalence of OMD among older adults in mainland China was significantly high. Early detection and effective intervention of OMD in older adults have public health and clinical importance.

Prevalence of High Non-high-density Lipoprotein Cholesterol and Associated Risk Factors in Patients with Diabetes Mellitus in Jilin Province, China: A Cross-sectional Study.

Dyslipidemia is a risk factor for cardiovascular diseases (CVDs) in patients with diabetes, and non-high-density lipoprotein cholesterol (non-HDL-C) is a better predictor of CVDs than low-density lipoprotein cholesterol (LDL-C) in patients with diabetes. Therefore, we aimed to investigate the distribution of non-HDL-C and the prevalence of high non-HDL-C level in Chinese patients with diabetes mellitus and identify the associated risk factors. Non-HDL-C concentration positively correlated with total cholesterol, triglycerides, and LDL-C concentrations. Although both non-HDL-C and LDL-C concentration both related positively with TC concentration, the magnitude of correlation was relatively higher for non-HDL-C. The prevalence of high non-HDL-C (⋝4.14 mmol/L) was higher in two age groups (55-64 years: 46.7%; 65-79 years: 47.3%) than other age groups (18-24 years: 4.2%; 25-34 years: 43.6%; 35-44 years: 38.1%; 45-54 years: 41.0%). It was also higher among overweight (45.1%), generally obese (50.9%), or abdominally obese (47.3%) subjects, compared with normal weight subjects (34.5%). The risk of high non-HDL-C increased with advancing age. Both general obesity [odds ratio (OR)=1.488, 95% confidence interval (CI): 1.003-2.209] and abdominal obesity (OR=1.561, 95% CI: 1.101-2.214) were significantly associated with high non-HDL-C levels.

Dyslipidemia awareness, treatment, control and influence factors among adults in the Jilin province in China: a cross-sectional study.

BACKGROUND: In China, even though the prevalence of dyslipidemia among adults increased yearly and dyslipidemia being an important risk factor for cardiovascular diseases among the Chinese population, however, the awareness, treatment and control of dyslipidemia are at low levels, and only limited studies on the influence factors associated with the awareness, treatment and control dyslipidemia in China have been carried out. METHODS: The analysis was based on a representative sample of 7138 adult subjects aged 18~79 years recruited from a cross-sectional study of chronic disease and risk factors among adults in the Jilin province in 2012. Chi-square test was used to compare the rates of dyslipidemia awareness, treatment and control between different characteristics of participants. Multiple logistic regression analyses were performed separately for each group to explore the associations between participants' characteristics and dyslipidemia awareness, treatment and control. RESULTS: Among participants with dyslipidemia, 11.6% were aware of the diagnosis, 8.4% were receiving treatment, and 34.8% had dyslipidemia controlled. Increase in age and BMI ≥ 24 kg/m2 were by far the strongest risk factors associated with better awareness and treatment of dyslipidemia. Retirees were more likely to be aware of their dyslipidemia condition (OR=1.255; 95% CI: 1.046, 1.506) and to be receiving treatment (OR=1.367; 95% CI: 1.114, 1.676) than manual workers. A family history of dyslipidemia increased the likelihood of awareness (OR=3.620; 95% CI: 2.816, 4.653) and treatment (OR=3.298; 95% CI: 2.488, 4.371) of dyslipidemia. Alcohol drinking and physical activity were associated with a lower level of awareness and treatment.Cigarette smokers (OR=0.501; 95% CI: 0.349, 0.719) and those with BMI ≥ 24 kg/m2 (OR=0.480; 95% CI: 0.326, 0.706) who received treatment were also associated with poor dyslipidemia control. CONCLUSION: Our study highlights low levels of awareness, poor treatment and control of dyslipidemia among adults aged 18~79 in the Jilin province. Promotion of healthy lifestyles and establishment of a comprehensive strategy of screening, treatment and control of dyslipidemia is needed to reduce or prevent the risk of cardiovascular disease in the Jilin province.

Increasing incidence of hemorrhagic fever with renal syndrome could be associated with livestock husbandry in Changchun, northeastern China.

BACKGROUND: Since the end of the 1990s, the incidence of hemorrhagic fever with renal syndrome (HFRS) has been increasing dramatically in Changchun, northeastern China. However, it is unknown which, and how, underlying risk factors have been involved in the reemergence of the disease. METHODS: Data on HFRS cases at the county scale were collected from 1998 to 2012. Data on livestock husbandry including the numbers of large animals (cattle, horses, donkeys and mules), sheep, and deer, and on climatic and land cover variables were also collected. Epidemiological features, including the spatial, temporal and human patterns of disease were characterized. The potential factors related to spatial heterogeneity and temporal trends were analyzed using standard and time-series Poisson regression analysis, respectively. RESULTS: Annual incidence varied among the 10 counties. Shuangyang County in southeastern Changchun had the highest number of cases (1,525 cases; 35.9% of all cases), but its population only accounted for 5.6% of the total population. Based on seasonal pattern in HFRS incidence, two epidemic phases were identified. One was a single epidemic peak at the end of each year from 1988 to 1997 and the other consisted of dual epidemic peaks at both the end and the beginning of each year from 1998 to the end of the study period. HFRS incidence was higher in males compared to females, and most of the HFRS cases occurred in peasant populations. The results of the Poisson regression analysis indicated that the spatial distribution and the increasing incidence of HFRS were significantly associated with livestock husbandry and climate factors, particularly with deer cultivation. CONCLUSIONS: Our results indicate that the re-emergence of HFRS in Changchun has been accompanied by changing seasonal patterns over the past 25 years. Integrated measures focusing on areas related to local livestock husbandry could be helpful for the prevention and control of HFRS.

Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and first-episode patients with schizophrenia in a Chinese Han population.

BACKGROUND: Angiotensin-converting enzyme (ACE), a key enzyme of the renin-angiotensin system, can modulate dopamine turnover in the midbrain. Previous studies have revealed an association between ACE gene insertion/deletion (I/D) polymorphism and chronic schizophrenia, yet results are conflicting. OBJECTIVE: The primary objective of this study was to examine whether the ACE gene I/D polymorphism is associated with first-episode patients with schizophrenia (FEP) in a Chinese Han population. METHODS: The presence of the polymorphism was determined in 220 FEP and 538 healthy controls using a case-control design. We assessed the psychopathology in 212 FEP using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The allelic and genotypic frequencies of the ACE gene I/D polymorphism did not significantly differ between FEP and healthy controls (both p>0.05). However, the negative PANSS symptom was significantly higher in FEP with the D/D genotype than those with I/D and I/I genotypes (all p<0.05) even after Bonferroni corrections (all p<0.05). Furthermore, the D allele of the ACE gene was associated with higher negative PANSS symptom score in FEP. CONCLUSIONS: Our results indicated that even though the ACE gene I/D polymorphism did not associate with FEP, it may play a role in susceptibility to the negative PANSS symptom of FEP in a Chinese Han population.

Antioxidant and antigenotoxic activity of bioactive extracts from corn tassel.

This study is designed to evaluate antioxidant and antigenotoxic activities of corn tassel extracts (CTTs). The major bioactive components of CTTs include flavonoid, saponin and polysaccharide. The antioxidant properties of the three bioactive components of CTTs were investigated by Ferric Reducing Antioxidant Property (FRAP) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assays. The activities of the extracts were determined by assessing the inhibition of mutagenicity of the direct-acting mutagen fenaminosulf, sodium azide, and indirect-acting mutagen 2-aminofluorene using the Ames test (strains TA98 and TA100). The results showed that the extraction rates of flavonoid, saponin, and polysaccharide from the dried corn tassels were 1.67%, 2.41% and 4.76% respectively. DPPH and FRAP assay strongly demonstrated that CTTs had antioxidant properties. CTTs at doses of 625, 1250 and 2500 µg per plate reduced 2-aminofluorene mutagenicity by 12.52%, 28.76% and 36.49% in Salmonella typhimurium TA98 strain assay respectively and by 10.98%, 25.27% and 37.83%, at the same doses in Salmonella typhimurium TA100 assay system, respectively. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay showed that the different concentrations of CTTs inhibited the proliferation of MGC80-3 cells in a dose-dependent manner (P<0.01). It is concluded that these integrated approaches to antioxidant and antigenotoxicity assessment may be useful to study corn tassel as a natural herbal material.

Association between DBH 19 bp insertion/deletion polymorphism and cognition in first-episode schizophrenic patients.

Many genes associated with dopamine (DA) and norepinephrine (NE) systems influence cognitive deficits of schizophrenia patients, but one key enzyme is dopamine beta-hydroxylase (DBH), which converts DA to NE and whose activity and levels are under strong genetic control. This study examines the association of the 19 bp insertion/deletion (Ins/Del) polymorphism in the 5' flank of the DBH gene with cognitive deficits in first-episode schizophrenic patients (FEP). We assessed the cognitive function in 195 FEP and 304 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The 19 bp Ins/Del polymorphism of DBH gene was genotyped. Our results showed that the allelic and genotypic frequencies of the 19 bp Ins/Del polymorphism significantly differed between FEP and healthy controls (both p < 0.05). Cognitive test scores were significantly lower in FEP than healthy controls on all scales (all p < 0.001) except for the visuospatial/constructional index (p > 0.05). Immediate memory abilities significantly differed by genotype (p<0.05) but not genotype×diagnosis. Immediate memory score was lower in FEP with DBH5'-Del/Del genotype (61.3 ± 17.2) than those with DBH5'-Ins/Ins genotype (68.6 ± 16.2; p < 0.05). The 19 bp Del allele was associated with poorer immediate memory performance than the Ins allele in FEP (p < 0.05). However, healthy controls did not show any differences in cognitive function indices between the Ins and Del for either the allele or genotype of the 19 bp Ins/Del polymorphism. Our findings suggest that the DBH5'-Ins/Del polymorphism may play a role in susceptibility to FEP. The DBH5'-Ins/Del polymorphism may also influence immediate memory in FEP. Moreover, FEP had poorer cognitive function than healthy controls in all examined cognitive domains except for the visuospatial/constructional index.

Smoking and tardive dyskinesia in male patients with chronic schizophrenia.

Interactions between smoking and movement disorders include the contrasting associations of more cigarette smoking with reductions in Parkinson's disease and increases in tardive dyskinesia (TD) symptoms. Here we examine the relationship between smoking and TD in a large sample of inpatients with schizophrenia. We used cross-sectional naturalistic methods to analyze the prevalence and severity of neuroleptic-induced TD in relation to cigarette smoking among 764 male chronic and medicated inpatients meeting DSM-IV criteria for schizophrenia. We administered a detailed questionnaire including general information, medical and psychological conditions, and smoking behaviors. We evaluated TD severity using the abnormal involuntary movement scale (AIMS) and psychopathology using the Positive and Negative Syndrome Scale (PANSS). The main statistical analyses used cross-tabulations for the prevalence of TD by smoking and multivariate regression analyses for continuous measures (AIMS and PANSS). We found that the prevalence of TD did not significantly differ between smokers (41%=237/578) and non-smokers (37%=69/186). Secondary outcomes showed a significant association between the AIMS total score and age, duration of illness and hospitalization times. Thus, smoking was not associated with TD in male Chinese schizophrenics, but consistent with previous reports, older patients with a longer duration of illness and more hospitalizations showed greater severity of TD.

Decreased serum brain-derived neurotrophic factor levels in schizophrenic patients with tardive dyskinesia.

The pathogenesis of tardive dyskinesia (TD) may involve neurodegeneration and associated dysfunction of brain-derived neurotrophic factor (BDNF) for the survival and maintenance of function in neurons. We therefore compared serum BDNF levels in schizophrenic patients with (n=129) and without TD (n=235), and normal controls (n=323). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Our results were that patients with TD had lower serum BDNF levels than those without TD and normals. Lower serum BDNF levels were correlated with greater PANSS negative subscores, but not correlated with the AIMS scores. Serum BDNF levels did not differ between patients on typical and atypical antipsychotics and were not correlated with antipsychotic doses or years of exposure. We concluded that decreased BDNF levels might be associated with TD pathophysiology and more negative symptoms of schizophrenia.

[Distribution and enrichment of nutrients in superficial sediment in Tianjin typical waters].

Concentrations of organic matter (OM), total nitrogen (TN), total phosphorus (TP) and bioavailable phosphorus (BAP) were determined in superficial sediment (0-25 cm) collected from 4 selected typical waters (Yuqiao reservoir, Haihe River, Haihe estuary and Bohai Bay) in Tianjin, China. Pollution index (P(i)) and enrichment factors (EF) were taken to analyze nutrients enrichment and dynamic characteristic. The results show that 4 typical waters are polluted by anthropogenic source and much higher than the permissible limits which most benthos can bearing, the concentrations of OM, TN, TP and BAP are decreasing progressively by the order: Haihe River > Haihe estuary> Bohai Bay Tianjin Sea Area. EF for OM, TN, TP and BAP reaches 1.6-6.5, 0.9-2.7, 0.9-2.6 and 4.4-9.2, respectively. The concentrations of BAP in different waters are inconsistent with those of TP, the ratio of BAP to TP in Yuqiao reservoir is the biggest, 16.3%, which shows endogenous source release is serious and eutrophication is the key problems of water pollution. The concentrations of OM and BAP increase in large scale between 1988 and 2005, TP basically keeps unchanging and TN slightly increases. Around Haihe River sediment dredging, nutrient concentrations (OM, TN and TP) of superficial sediments in Haihe River reduce to 57.7%, 82.8% and 85.2% of original concentration, respectively. And sediment dredging plays a positive role in nutrients removal.

[Association between polymorphism of BDNF and internalizing disorders].

OBJECTIVE: To investigate the genetic association between brain-derived neurotrophic factor (BDNF) gene polymorphism and internalizing disorders, to provide the theoretical basis to explore the etiology of internalizing disorders. METHODS: PCR-based ligase detection reaction (PCR-LDR) was applied to tag single nucleotide lengh polymorphism (SNPs) of BDNF gene among 259 undergraduates affected by internalizing disorders and 269 healthy undergraduates. Haplotype analysis and multiple locus analysis were conducted to analyze the genotyping data. RESULTS: The genotypic frequency of tag SNPs of BDNF gene did not deviate from Hardy-Weinberg equilibrium in both case and control groups. Rs12273539 was not associated with internalizing disorders (P > 0.05), but rs10835210 and rs2030324 were related to internalizing disorders (P < 0.05). The case group had more A allele of rs10835210 and C allele of rs2030324 when compared to the controls while A allele of rs10835210 and C allele of rs2030324 seemed to be the risk factors of internalizing disorder (OR = 1.877, P < 0.001; OR = 1.347, P < 0.05). Results of multiple locus analysis showed that the haplotype composed by the three tag SNPs which was related to internalizing disorders (chi(2) = 23.537, P < 0.001). CONCLUSION: BDNF gene might serve as the susceptible gene for internalizing disorder.

[Study on the genetic association between the polymorphism of cytosolic phospholipase A2 family genes and schizophrenia].

OBJECTIVE: To investigate the genetic association between the polymorphism of cytosolic phospholipase A2 (cPLA2) family genes and schizophrenia in the North Han Chinese. METHODS: Method of polymerase chain reaction-based ligase detection reaction (PCR-LDR) was applied to genotype 10 single nucleotide polymorphisms (SNPs) of cPLA2 family genes among 201 pedigrees consisting of fathers, mothers and affected offsprings with schizophrenia. Haplotype relative risk (HRR) test, transmission disequilibrium test (TDT), haplotype transmission analysis and multiple locus analysis were conducted to analyze the genotyping data. RESULTS: The genotypic frequency of cPLA2 gene did not deviate from Hardy-Weinberg equilibrium in both case and control groups. HRR and TDT showed that the 10 SNPs were not associated with schizophrenia (P > 0.05). Analysis for haplotype transmission showed that no haplotype systems was associated with schizophrenia (P > 0.05). Results from COA and COG tests showed a disease association for the rs2162886-rs1668589, rs891014-rs1668589 and rs2307279-rs7542180 combinations (chi2 = 6.913, P = 0.032; chi2 = 8.393, P = 0.015; chi2 = 8.447, P = 0.038). CONCLUSION: Many loci in the cPLA2 family genes were associated with schizophrenic.

Is KPNB3 locus associated with schizophrenia?

OBJECTIVE: To reconfirm the association of KPNB3 with schizophrenia in Chinese population. METHODS: Two single nucleotide polymorphisms (SNPs), rs2588014 and rs626716 at the KPNB3 locus, were genotyped in 304 Chinese Han family trios consisting of fathers, mothers, and affected offsprings with schizophrenia. These 2 SNPs were detected by PCR-based restriction fragment length polymorphism (RFLP) analysis. The Hardy-Weinberg equilibrium for genotypic distributions was estimated by the goodness-of-fit test. The UNPHASED program was used to perform transmission disequilibrium test (TDT), haplotype analysis, and pair-wise measure of linkage disequilibrium (LD) between these 2 SNPs. RESULTS: The genotypic distributions of both rs2588014 and rs626716 were in the Hardy-Weinberg equilibrium (P > 0.05). The TDT revealed allelic association with rs626716 (chi2 = 9.31, P = 0.0023) but not with rs2588014 (chi2 = 3.44, P = 0.064). The global P-value was 0.0099 for 100 permutations. The haplotype analysis also showed a disease association (chi2 = 25.97, df = 3, P = 0.0000097). CONCLUSION: The present study provides further evidence in support of the KPNB3 association with schizophrenia in Chinese population.

Searching for a schizophrenia susceptibility gene in the 22q11 region.

OBJECTIVE: To investigate a genetic association for schizophrenia within chromosome 22q11 in a Chinese Han population. METHODS: The PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis was used to detect three single nucleotide polymorphisms (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change) present in the ARVCF (armadillo repeat gene deletion in velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979 (expressed sequence tags, EST) locus, among 100 Chinese family trios consisting of fathers, mothers and affected offspring with schizophrenia. Genotype data were analyzed by using linkage disequilibrium (LD) methods including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and haplotype transmission analysis. RESULTS: The genotype frequency distributions of three SNPs were all in Hardy-Weinberg equilibrium (P>0.05). Both the HRR and the TDT analysis showed that rs165815 was associated with schizophrenia (chi2=6.447, df=1, P=0.011 and chi2=6.313, df=1, P=0.012, respectively), whereas the other two SNPs did not show any allelic association. The haplotype transmission analysis showed a biased transmission for the rs165655-rs165815 haplotype system (chi2=17.224, df=3, P=0.0006) and for the rs756656-rs165655-rs165815 hapoltype system (chi2=20.965, df=7, P=0.0038). CONCLUSION: Either the ARVCF gene itself or a nearby locus may confer susceptibility to schizophrenia in a Chinese Han population.

[Searching for a schizophrenia susceptibility gene in the 22q11 region].

OBJECTIVE: To investigate the genetic association for schizophrenia within the long arm region 1 band 1 of chromosome 22 (22q11) in a Han Chinese population. METHODS: Polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis was used to detect three single nucleotide polymorphism (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change) present in the ARVCF (armadillo repeat gene deletion in velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979 (expressed sequence tags, EST) locus, among 100 nuclear families composed of fathers, mothers and affected offspring with schizophrenia. Genotyping data were analyzed by linkage disequilibrium methods including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and haplotype transmission analysis. RESULTS: The genotype frequency distributions of three SNPs were all in Hardy-Weinberg equilibrium; Both HRR and TDT analysis showed that rs165815 was associated with schizophrenia (P < 0.05), whereas the other two SNPs did not show any allelic association. The haplotype transmission analysis showed a biased transmission for the rs165655-rs165815 haplotype system and for the rs756656-rs165655-rs165815 haplotype system (P < 0.01). CONCLUSION: Either ARVCF gene itself or a nearby locus might confer susceptibility to schizophrenia in a Han Chinese population.