polymorphism

摘要： The val66met polymorphism of the bdnf gene, which is associated with compromised brain-derived neurotrophic factor (BDNF) signaling, impaired synaptic plasticity, and impaired learning, may increase one’s susceptibility to stress- and anxiety-related disorders. Indeed, previous work has reported greater anxiety-related behaviors and impairments of fear conditioning and extinction in individuals who carry the met allele that results from this polymorphism. Nevertheless, findings in this area of research have been equivocal. Thus, we examined the influence of the val66met polymorphism on fear conditioning, extinction, and extinction memory testing. One hundred and twenty healthy participants completed differential fear conditioning in a fear-potentiated startle paradigm, followed by extinction and extinction memory testing 24 and 48 hr later, respectively. Participants were genotyped for the val66met polymorphism and divided into met allele carriers and non-carriers. Results revealed that, although both met-carriers and non-carriers developed conditioned fear, met-carriers exhibited significantly weaker fear acquisition than non-carriers. This difference persisted throughout extinction and extinction memory testing and, during these last two days of testing, was primarily evident in females. These results are consistent with previous work demonstrating that this polymorphism is associated with impaired amygdala-dependent fear learning and extend such findings by demonstrating that females may be more sensitive to such effects.

摘要： The association between type 2 diabetes mellitus(DM)and colorectal cancer(CRC)has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients.The association between DM and the survival of patients with CRC is controversial.Evidence suggests that metformin with its anti-inflammatory effects is a protective factor against the development of CRC among DM patients and that metformin therapy is associated with a better prognosis in patients with DM.In our cohort,we did not find any associations between the presence of DM or metformin and cancer specific survival or any relation to plasma levels of a panel of 40 inflammatory factors and irisin.On the other hand,we identified that the insulin-like growth factor binding protein 7 single nucleotide polymorphism rs2041437 was associated with DM in CRC patients.The dominance of the T bearing genotypes in patients with DM was statistically significant(P=0.038),with an odds ratio of 1.66(95%confidence interval:1.03-2.69).

摘要： In most eukaryotes,oxidative phosphorylation(OXPHOS)is the main energy production process and it involves both mitochondrial and nuclear genomes.The close interaction between the two genomes is critical for the coordinated function of the OXPHOS process.Some bivalves show doubly uniparental inheritance(DUI)of mitochondria,where two highly divergent mitochondrial genomes,one inherited through eggs(F-type)and the other through sperm(M-type),coexist in the same individual.However,it remains a puzzle how nuclear OXPHOS genes coordinate with two divergent mitochondrial genomes in DUI species.In this study,we compared transcription,polymorphism,and synonymous codon usage in the mitochondrial and nuclear OXPHOS genes of the DUI species Ruditapes philippinarum using sex-and tissue-specific transcriptomes.Mitochondrial and nuclear OXPHOS genes showed different transcription profiles.Strong co-transcription signal was observed within mitochondrial(separate for F-and M-type)and within nuclear OXPHOS genes but the signal was weak or absent between mitochondrial and nuclear OXPHOS genes,suggesting that the coordination between mitochondrial and nuclear OXPHOS subunits is not achieved transcriptionally.McDonald-Kreitman and frequency-spectrum based tests indicated that M-type OXPHOS genes deviated significantly from neutrality,and that F-type and M-type OXPHOS genes undergo different selection patterns.Codon usage analysis revealed that mutation bias and translational selection were the major factors affecting the codon usage bias in different OXPHOS genes,nevertheless,translational selection in mitochondrial OXPHOS genes appears to be less efficient than nuclear OXPHOS genes.Therefore,we speculate that the coordination between OXPHOS genes may involve post-transcriptional/translational regulation.

摘要： Introduction: DNA repair enzymes continuously monitor DNA to correct damaged nucleotide residues generated by exposure to environmental mutagenic and cytotoxic compounds or carcinogens. Our objective was to investigate the association among XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD-ERCC2 (Lys751Gln), APE1 (Asp241Glu), PARP-ADPRT (Val762Ala) DNA repair gene polymorphisms and lung cancer in Turkish population. Materials and Methods: Our patient group consists of 90 patients with lung cancer and the control group had 100 healthy individuals all of those smoking. DNA was extracted using the whole blood samples. PCR- RFLP technique was used to investigate the polymorphisms on target genes. Results: There was no significant difference in the genotype distributions of XPD Lys751Gln, XRCC1 Arg194Trp, XRCC3 Thr241Met, APE1 Asp241Glu between lung cancer patients and controls for each polymorphism (p > 0.05). However, there was a significant difference between the genotype distributions of XRCC1 Arg399Gln, and PARP Val762Ala in patients and the control group (p > 0.05). Discussion: Only the polymorphisms of XRCC1 codon 399 and PARP Val762Ala alleles are associated with the risk of lung cancer. Other genotypes were not related to lung cancer.

摘要： Introduction: Polymorphisms are the main genetic factors associated with toxicities of antituberculosis drugs. This literature review summarizes the polymorphisms of the genes that code for the enzymes of the metabolism of antituberculosis drugs and their transmembrane transporters. Some mechanisms of drug-associated toxicities and strategies for their management have also been described in this review. Methods: The bibliographic searches were exclusively carried out in PubMed, over a period of ten years (2010-2020). The search terms were the words “toxicity + antituberculosis drug + one or two word(s) among the following: polymorphism, genetics, mutation, SNP, HLA or haplotype”. Publications in English or French, relating to the various toxicities associated with first-line anti-tuberculosis drugs (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) administered to patients with pulmonary tuberculosis, extrapulmonary tuberculosis or co-infected with TB/HIV were included in this review. Duplicates, in vitro, in silico or drug-induced toxicity studies other than antituberculosis drugs and genetic mutations of Mycobacteria strains were not included. Results: The studies selected and included were case reports, cohort studies, original research, systematic reviews and meta-analyses on human subjects of different ethnic origins. Hepatotoxicity is the most common toxicity associated with NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms in patients on antituberculosis drugs. Other forms of toxicity, less frequent, occurring in certain patients under concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), antiretrovirals (ARVs), antibiotics or antiepileptics have also been identified. Conclusion: The genetic polymorphisms associated with the toxicities of antituberculosis drugs concern both the main enzymes of the metabolic pathways (NAT2, CYP2E1, GST) and the transmembrane transporters (SLCO1B1 and ABCB1). Other genetic polymorphisms (TXNRD1, SOD2, TYMP) have been suspected but their mechanisms are not yet well understood.

摘要： SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic (PK). The objective of this study was to identify in African patients with tuberculosis (TB) or TB/HIV co-infection, the SLCO1B1 and NAT2 polymorphisms, associated with the variability of Rifampicin and Isoniazid pharmacokinetic. TB or TB/HIV co-infected patients from Benin, Guinea, Senegal, and South Africa were included in this study. The blood samples collected were stored at -80˚C until DNA extractions. The DNA extracts were then frozen at -80˚C after quality control. Double stranded DNA of the samples were quantified using a fluorimetric method to select suitable samples for the preparation of 96-well microplates, containing 100 μl of DNA extract per well at the concentration of 20 ng/μl. Illumina HumanOmniExpress-24 v1.2 microarray genotyping was performed by an external vendor. The genotyping data were analyzed and the polymorphisms with a call rate < 95% or presenting a departure from the Hardy-Weinberg Equilibrium (HWE) were excluded. The correlation between significant genetic polymorphisms, the clearance, and the AUC were tested by a multiple linear regression model using the PLINK2 software. Out of 385 samples, five (05) were excluded after quality controls. After the frequency test, 384,586 SNPs failed the Hardy-Weinberg Equilibrium. Finally, 378 samples and 318,751 SNPs were included in the genetic analyses. The SLCO1B1 and NAT2 polymorphisms were associated with the variability of Rifampicin and Isoniazid PK parameters. There are SLCO1B1 and NAT2 polymorphisms carriers among TB and TB/HIV co-infected patients from Sub-Saharan Africa.

摘要： rs6311 and rs6313 are two Single Nucleotide Polymorphisms (SNPs) on the Serotonin Receptor 2A gene (5-HTR2A) in complete linkage disequilibrium. Numerous gene association studies have examined the relationships between one or both of these two polymorphisms and Major Depressive Disorder (MDD), with conflicting results. The present meta-analysis examined 19 case-control gene association studies, 9 of which included rs6311 (n = 3382), and 15 of which included rs6313 (n = 5590). The strength of relationship with MDD was assessed by pooled odds ratios and 95% confidence intervals for both SNPs according to four genetic models. Heterogeneity was measured by Q and I2. Subgrouping was performed by minor allele and by ethnicity. Results were nonsignificant for all models and subgroups, suggesting that genotype alone does not play a major role in genetic susceptibility to depression. The potential for epistatic, epigenetic, and regulatory RNA interactions with these SNPs is discussed, and future areas of research are recommended.

摘要： Background: Rheumatoid arthritis (RA) is a common autoimmune disease in which a combination of risk alleles from different susceptibility genes predisposes the patients to develop clinical symptoms following exposure to environmental factors. RA is a chronic and progressive disease characterized by synovial inflammation that results in destruction in the affected joints and severe problems in individual’s mobility. Several immune-related risk factors have been associated with RA, these include single nucleotide polymorphisms (SNPs) in cytokine genes. The impact of these cytokine gene polymorphisms is due to their association either with elevated serum levels and/or variations in their serum levels are associated with disease-onset and progression. The objective of this study was to investigate the role of Interleukin-6 (IL6), Interleukin-13 (IL13) and Tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms in genetic susceptibility of RA in Kuwaiti patients. Methods: We have determined the genotypes of IL6 gene (-174G/C;rs1800795), IL13 gene (R130Q;rs20541) and TNF-alpha gene (-308A/G' rs1800629) polymorphisms in 192 Kuwaiti patients with RA and compared it to that in 104 healthy controls. The diagnosis of RA was based on the American College of Rheumatology (ACR) classification criteria. The genotypes for IL6, IL13 and TNF-alpha gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods and confirmed by DNA sequencing. Results: The frequency of IL6 gene (-174G/C;rs1800795) and TNF-alpha gene (-308A/G' rs1800629) polymorphisms manifested a statistically significant difference between Kuwaiti RA patients and controls (P = 0.02 and 0.002 respectively). In contrast, the frequency of IL13 gene (R130Q;rs20541) polymorphism did not show a significant difference between Kuwaiti RA patients and controls. Conclusions: Our data showed an association of two cytokine gene polymorphisms (i.e. IL6 gene -174G/C;rs1800795 polymorphism, and TNF-alpha gene -308A/G, rs1800629 polymorphism) with RA in Kuwaiti patients highlighting their significant contribution in genetic susceptibility of this chronic disease possibly along with other factors.

摘要： Haptoglobin(Hp)is an acidic glycoprotein,existing in the serum and other body fluids of human beings and a variety of mammals.Hp is produced in the liver,white adipose tissue,and the kidney.The genetic polymorphisms and different phenotypes of Hp have different biological functions.Hp has antibacterial,antioxidant,and angiogenic effects and is associated with multiple diseases including simple obesity,vascular complications of diabetes mellitus,nonalcoholic fatty liver disease,hypertension,blood diseases,autoimmune diseases,and malignant tumors.Hp also participates in many life activities,indicating the importance of Hp in further studies.Previously,we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials.However,the specific mechanism of Hp in patients with simple obesity is still unclear.The purpose of this article is to introduce recent research progress on Hp,emphasizing the relationship between Hp and the development of metabolic disease,which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.

摘要： Male Breast Cancer (MBC) has a familial component thus identification of polymorphic risk alleles of candidate genes and/or cytogenetic anomalies may help to predict the risk for the offspring of MBC patients. The conventional metaphase cytogenetics can indicate loci that are hotspots while analysis by single nucleotide polymorphism arrays (SNP-A) can identify chromosomal defects which may play a role in the etiology of cancer. A cumulative genotype risk due to each allele of candidate genes of the signaling pathways regulating c-MYC, HIF1A, TP53 and BRCA1 may be a factor facilitating cancer development. Cancer risk was assessed in a 35-year-old healthy son of a 60-year-old MBC patient with a family history of cancer by metaphase cytogenetics, SNP-A and analysis of 25 polymorphisms in six genes TP53, MDM2, VEGF, VEGFR1, HIF1A, and BRCA1. The risk genotype GG-TT of MDM2 309T > G and VEGF-417C/T polymorphisms along with chromosomal instability shown by cytogenetic analysis and SNP-A, rare de novo duplication Yp, deletion in 7q pericentromeric region indicate an increased risk of cancer in the healthy son of an MBC patient.

摘要： Lack of an association between Alzheimer's disease and the cystatin C (CST3) gene G73A polymorphism in Mainland Chinese. Dement Geriatr Cogn Disord. 2008;25(5):461-4. Alzheimer's disease (AD) is a complex multifactorial disorder involving a number of genetic and environmental factors. Cystatin C (CST3)，which belongs to the type II cystatin gene family，is a potent inhibitor of lysosomal proteinaseso Immunohistochemical studies have demonstrated the colocalization of the β-amyloid (A-beta) and cystatin C peptides within arteriolar walls in the AD brain. The G73A polymorphism of the CST3 genemay be associated with AD development. To investigate a possible association between the CST3 G73A polymorphism and late-onset AD (LOAD) in Mainland Chinese，we examined 281 LOAD patients and 376 healthy controls. All subjects were genotyped for CST3 and apolipoprotein E (APOE). There were no significant differences in the CST3 genotype or allele frequencies between the cases and the controls. Likewise，with the stratification of the APOE epsilon4 status，no statistical difference was observed between the cases and the controls. Our findings suggest that this polymorphism may not represent an additional genetic risk factor for LOAD in Mainland Chinese.

摘要： 本文利用PCR-SSCP技术对113头郏县红牛CLPG基因的多态性进行了分析.发现有三个等位基因A、B、C,他们的基因频率分别为0.8673,0.0619和0.0708.仅发现AA、AB和AC三种基因型,频率分别为0.7345,0.1239,0.1416.群体的杂合度(Hk),有效等位基因数(Ne)、多态信息含量(PIC)分别为0.2389,1.1331和0.2256.该位点处于Hardy-Weinberg不平衡状态.

摘要： 本文利用PCR-SSCP技术对113头郏县红牛CLPG基因的多态性进行了分析.发现有三个等位基因A、B、C,他们的基因频率分别为0.8673,0.0619和0.0708.仅发现AA、AB和AC三种基因型,频率分别为0.7345,0.1239,0.1416.群体的杂合度(Hk),有效等位基因数(Ne)、多态信息含量(PIC)分别为0.2389,1.1331和0.2256.该位点处于Hardy-Weinberg不平衡状态.

摘要： 本文利用PCR-SSCP技术对113头郏县红牛CLPG基因的多态性进行了分析.发现有三个等位基因A、B、C,他们的基因频率分别为0.8673,0.0619和0.0708.仅发现AA、AB和AC三种基因型,频率分别为0.7345,0.1239,0.1416.群体的杂合度(Hk),有效等位基因数(Ne)、多态信息含量(PIC)分别为0.2389,1.1331和0.2256.该位点处于Hardy-Weinberg不平衡状态.

摘要： 本文利用PCR-SSCP技术对113头郏县红牛CLPG基因的多态性进行了分析.发现有三个等位基因A、B、C,他们的基因频率分别为0.8673,0.0619和0.0708.仅发现AA、AB和AC三种基因型,频率分别为0.7345,0.1239,0.1416.群体的杂合度(Hk),有效等位基因数(Ne)、多态信息含量(PIC)分别为0.2389,1.1331和0.2256.该位点处于Hardy-Weinberg不平衡状态.

摘要： 本文利用PCR-SSCP技术对113头郏县红牛CLPG基因的多态性进行了分析.发现有三个等位基因A、B、C,他们的基因频率分别为0.8673,0.0619和0.0708.仅发现AA、AB和AC三种基因型,频率分别为0.7345,0.1239,0.1416.群体的杂合度(Hk),有效等位基因数(Ne)、多态信息含量(PIC)分别为0.2389,1.1331和0.2256.该位点处于Hardy-Weinberg不平衡状态.

摘要： 本发明涉及一种Polymorph树脂制品及其制备方法，属于树脂制品技术领域。本发明的制品包括固型内芯和柔性外膜，所述固型内芯由polymorph树脂颗粒制成，所述柔性外膜预制为具有制品形状的套袋式膜层。本发明Polymorph树脂制品美观实用、制备工艺简单。