BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George’s Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (?3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of “BRCAness” in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP- ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

Research status of CHEK2 gene and breast cancer / 中国医师杂志

At present, breast cancer is one of the main causes of death for women in the world. In recent years, the incidence rate of breast cancer in China has also been rising. Existing studies have shown that the most fully studied gene for breast cancer susceptibility is breast cancer susceptibility gene 1/2 (BRCA1/2), and other genes related to the increased risk of breast cancer have also been confirmed, including cell-cycle-checkpoint kinase gene 2 (CHEK2), which is a tumor suppressor gene encoding serine/Threonine kinase CHEK2. The gene is involved in DNA repair, cell cycle regulation, apoptosis and other DNA damage response pathways. This article reviews the research status of CHEK2 gene and its important role in the prevention, diagnosis and treatment of breast cancer.

Efficacy and safety of olaparib in adjuvant therapy of BRCA1/2 mutated HER2-negative breast cancer：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of olaparib in adjuvant therapy of breast cancer susceptibility gene （BRCA） 1/2 mutated human epidermal growth factor receptor 2 （HER2）-negative breast cancer， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， ScienceDirect， the Cochrane Library and Embase databases， randomized controlled trials about adjuvant therapy of olaparib （trial group） versus adjuvant therapy of other drugs （control group） were collected. After literature screening and data extraction， meta-analysis， publication bias analysis and sensitivity analysis were performed by using RevMan5.4 software. RESULTS A total of 5 randomized controlled trials were included， with a total of 2 633 patients， including 1 495 cases in trial group and 1 174 cases in control group. Meta-analysis showed that in terms of efficacy， compared with control group， overall survival [HR＝1.02， 95%CI （1.01，1.03）， P＝0.000 8] and progression-free survival [HR＝1.78， 95%CI（1.46，2.17）， P＜0.000 01] were longer significantly in the trial group. In terms of safety， compared with the control group， the incidence of adverse drug reactions at any level in the trial group was higher [RR＝1.41， 95%CI （1.12， 1.78）， P＝0.004]， while there was no statistically significant difference in the incidence of adverse drug reactions above level 3 between the two groups [RR＝1.75， 95%CI （0.82， 3.74）， P＝0.15]. The results of publication bias indicated that the possibility of publication bias in this study was relatively low. The results of sensitivity analysis showed that the results obtained in this study were robust. CONCLUSIONS Compared with patients without adjuvant therapy of olaparib， adjuvant therapy of olaparib can prolong overall survival and progression-free survival of patients with BRCA1/2 mutated HER2-negative breast cancer，but the risk of adverse drug reactions is relatively high.

Progress of hereditary breast cancer with breast cancer susceptibility gene 1/2 mutations / 肿瘤研究与临床

Hereditary breast cancer refers to malignant tumors caused by pathogenic germline mutations of breast cancer susceptibility genes (BRCA). At present, it is believed that BRCA1/2 genes are most closely related to the development of hereditary breast cancer. Mutation will lead to loss of normal function, instability of genome, and then lead to tumorigenesis. Especially for those with germline mutations, not only the risk of breast cancer will be greatly increased, but also the probability of ovarian cancer and other cancers will be increased. With the emergence and clinical application of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, BRCA1/2 genes have been regarded as new targets for the treatment of breast cancer. This article reviews the latest research of breast cancer with BRCA1/2 gene mutations.

Effect of BRCA1 on proliferation, migration and invasion of non-small cell lung cancer H1650 cells via Wnt/β-catenin pathway / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of breast cancer susceptibility gene 1 (BRCA1) on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC) H1650 cells through Wnt/β-catenin pathway. Methods: WB and qPCR were used to detect the mRNA and protein expressions of BRCA1 in NSCLC A549, H1299, H1650 cells and normal lung epithelial BEAS-2B cell. A stable BRCA1 over-expression cell line (LV-BRCA1) was constructed in H1650 cells, and blank control group (NC), negative control group (LV-BRCA1-NC), experimental group (LV-BRCA1) and inhibitor group (LV-BRCA1+XAV-939) were set up. The proliferative activity of cells in each group was detected by MTT assay, the migration ability of cells was detected by scratch test, the invasive ability of cells was detected by Transwell method, and the protein expression levels of BRCA1, cyclin D1, β-catenin, c-Myc and Cox2 were detected by WB. Results: The mRNA and protein expression levels of BRCA1 in NSCLC cells were significantly higher than those in BEAS-2B cells (all P<0.01). Up-regulation of BRCA1 expression in H1650 cells could significantly enhance cell proliferation, migration and invasion (P<0.05 or P<0.01), and increase the protein expressions of cyclin D1, β-catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01). β-catenin inhibitor XAV-939 significantly down-regulated the proliferation, migration and invasion ability of H1650 cells over-expressing BRCA1, and decreased the protein expressions of cyclin D1, β-catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01). Conclusion: BRCA1 can promote the proliferation, migration and invasion of NSCLC H1650 cells by activating Wnt/β-catenin pathway, and it is expected to be a potential diagnostic biomarker and treatment target for NSCLC.

Design, synthesis, and biological evaluation of quinazolin-4(3H)-one derivatives co-targeting poly(ADP-ribose) polymerase-1 and bromodomain containing protein 4 for breast cancer therapy

@#This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.

Advances in the treatment of ovarian cancer with BRCA gene mutation / 中国综合临床

Ovarian cancer is the most fatal malignant tumor in female reproductive system tumors.In most women, it is diagnosed in a late stage, which largely leads to the poor prognosis of ovarian cancer.Breast cancer susceptibility gene (BRCA) is an important DNA homologous repair gene, which plays a major role in the normal cellular DNA repair mechanism.Its mutation will lead to homologous recombination defects, which will affect the stability of the genome and lead to occurrence of tumors.In recent years, BRCA genetic testing has become a key step in the risk assessment, prognosis, treatment and prevention of ovarian cancer.

Study on the relationship between synonymous mutation of ABCA3 gene and neonatal respiratory distress syndrome of mongolian and han nationality in inner mongolia / 中华急诊医学杂志

Objective:To investigate whether the synonymous variation of the ATP-binding cassette transporter A3 (ABCA3) gene may increase the risk of respiratory distress syndrome (RDS) in Mongolian and Han newborns in Inner Mongolia.Methods:From January 2018 to June 2019, the children of Mongolian and Han nationality who were hospitalized in the Department of Neonatal Pediatrics, affiliated Hospital of Inner Mongolia Medical University and the control group were sequenced by ABCA3 exon gene to analyze whether there was synonymous mutation in ABCA3 gene.Results:A total of 101 children with RDS were enrolled, including 37 children with Mongolian and 64 with Han children. There were 113 patients in the control group, including 45 Mongolian children and 68 Han children. Children with Mongolian and Han nationality RDS and control group can detect multiple synonymous mutation sites, such as: F353F, P585P, A227A, V150V, L982L, A928A, S1372S, P1653P, E1618E, and A1027A, etc, among them, four synonymous variants of p.A227A, p.F353F, p.P585P and p.S1372S are common synonymous mutants. In both Mongolian and Han nationality, the frequency of ABCA3 gene synonymous mutation in RDS group was significantly higher than that in control group (Mongolian: χ2=9.402, P=0.002; Han: χ2=9.348, P=0.002 ). The mutation rates of F353F and P585P in Mongolian and Han children with RDS were higher than those in the control group, and the difference was statistically significant(Mongolian F353F: χ2=5.270, P=0.022; Han F353F: χ2=5.532, P=0.019.Mongolian P585P: χ2=4.711, P=0.030; Han P585P: χ2=4.480, P=0.034). Conclusions:The synonymous variation of ABCA3 gene may increase the risk of RDS in Mongolian and Han newborns in Inner Mongolia, and F353F and P585P may be one of the susceptible genes of RDS in Mongolian and Han newborns in Inner Mongolia.

Correlation of BRCA1 gene polymorphism with chemosensitivity and prognosis of metastatic esophageal squamous cell carcinoma treated with cisplatin combined with capecitabine / 中国临床药理学与治疗学

AIM: To explore the effect of single nucleotide polymorphism (SNP) of breast cancer susceptibility gene 1 (BRCA1) on chemotherapy sensitivity and survival prognosis of patients with metastatic esophageal squamous cell carcinoma. METHODS: A total of 153 patients with newly treated metastatic esophageal squamous cell carcinoma who were admitted to Suzhou Science and Technology City Hospital from June 2016 to February 2020 were included and administered with cisplatin combined with capecitabine chemotherapy. Before the first chemotherapy, 5 mL of venous blood was collected to extract DNA, and the TaqMan probe method was used to detect the genotypes of the BRCA1 gene rs8176318G/T, rs799917T/C and rs1799966T/C polymorphic loci. The objective response rate (ORR) and overall survival (OS) of different genotypes were analyzed. RESULTS: Rs799917T/C polymorphism was closely related to the chemosensitivity of metastatic esophageal squamous cell carcinoma. The chemotherapy response rates of TT, TC and CC genotypes increased gradually (TT 22.5%, TC 38.6%, CC 55.3%, χ

Role of long noncoding RNA AC073046.25 in regulation of systemic lupus erythematosus susceptibility gene TET3 expression / 上海交通大学学报（医学版）

Objective: To investigate the regulatory effect of long noncoding RNA (lncRNA) AC073046.25 on the expression of Tet methylcytosine dioxygenase 3 (TET3) in monocytes, and analyze the feasibility of AC073046.25 as a biomarker for the diagnosis of systemic lupus erythematosus (SLE). Methods: The cell specificity and function of AC073046.25 were predicted by epigenetic modification and cytoplasm/nuclear location experiment. In U-937 cells, antisense oligonucleotide (ASO) was used to knock down AC073046.25. The effect of ASO knockdown on TET3 expression was analyzed by quantitative real-time PCR. Monocytes from healthy volunteers (n=32) and SLE patients (n=46) were collected. The correlation between AC073046.25 and TET3 expression was analyzed by Pearson coefficient. Healthy volunteers were included in the healthy control group, and the SLE patients were divided into SLE-inactive group and SLE-active group according to the systemic lupus erythematosus disease activity index (SLEDAI). The differences of AC073046.25 and TET3 expression in healthy control group and different disease activity groups were compared by unpaired bilateral student's t test. Results: The epigenetic modification and cytoplasm/nuclear location experiment showed that AC073046.25 may be involved in the regulation of TET3 expression in monocytes. In U-937 cells, after ASO knocked down AC073046.25, TET3 expression level decreased (both P=0.002 in ASO groups). Correlation analysis showed that AC073046.25 expression was positively correlated with TET3 expression in primary monocytes (r=0.650, P=0.000). Unpaired bilateral student's t test showed that the expression level of AC073046.25 in the SLE-active group was lower than that in the healthy control group (P=0.002) and the SLE-inactive group (P=0.000). Conclusion: In monocytes, AC073046.25 can regulate the expression of TET3, and its expression is significantly decreased in monocytes derived from disease active SLE patients, which implicating that AC073046.25 can be thought as a biomarker for SLE disease activity diagnosis.

Development and evaluation of thrombosis susceptibility gene chip / 吉林大学学报(医学版)

Objective: To explore the development methods and prelimnary clinical validation of thrombos susceptibility gene chip, and to illustrate a rapid and high-throughput method for detecting the thrombos susceptibility gene mutation. Methods: According to the published gene sequences of thrombotic susceptibility genes in GenBank, the reference probes and special probes were pointed on the glass slide. After ultraviolet crosslinking, thrombois susceptibility gene chip was eatablished. The validity of gene chip was tested by potive reference (mutant gene and normal gene at each detection site) and negative reference (distilled water) as templates, thereby performing PCR reaction. The specificity and sensitivity of gene chip were detected by using the human genome DNA of target sequence proven by sequencing as templates, thereby performng PCR reaction. Meanwhile 150 healthy subjects and 24 thrombosis patients with family hstory of unexplained thrombotic dsease from Jilin province, Henan provnce and Yunnan province were carried out the clinical verification of gene chip. The analyss index was the hybridization signal trength of the correspondng ite. Results: The hybridization results of postive reference and negative reference as templates showed that the specific hybridization signals appeared at the corresponding ites, which indicated that the detection sites of gene chip are effective. The gene chip used to detect the selected mutation sites had specific hybridization signals, suggesng there were good specificity of gene chip. The senstivity of gene chip was 50 - 100 mg · L-1 by testng genomic DNA with stepwise dilution. Eight individuals with thrombosis susceptibility gene mutations were found in 150 healthy subjects. Twenty ndividuals with thrombosis susceptibility gene mutations were found in 24 thrombosis patients with family hstory of unexplaned thrombotic dsease. The statistcs results showed that the detection rate of thrombosis susceptibility gene mutations in the thromboss patients with unexplaned thrombotic disease family history was significantly higher than that of the healthy subjects (P<0.05). Conclusion: The developed thrombosis susceptibility gene chip has great specificity, senstivity, and high detection rate of thromboss susceptibility genes. It has potental values in the early dagnosis and susceptibility sk assessment of thrombotic dseases.

A study of susceptibility genes in rare monozygotic twins with generalized aggressive periodontitis / 口腔疾病防治

Objective@#Exploring the effects of susceptibility genes on aggressive periodontitis during its occurrence and development lays a foundation for further research on its genetic pathogenesis.@*Methods@#Medical history and clini⁃ cal indicators were collected from monozygotic twins with generalized aggressive periodontitis. Susceptibility genes were detected by polymerase chain reaction⁃restriction fragment length polymorphisms, and the exon gene components were analyzed by whole⁃exome sequencing. @*Results @#The severity of generalized aggressive periodontitis in the twins was dif⁃ ferent (P < 0.05). Florida diagnosis results showed that the younger sister’ s explored clinical depth (probing depth, PD) and clinical attachment loss (CAL) were higher than those for the elder sister, but her clinical bleeding index (bleeding on probing, BOP) was lower than that of the elder sister. In addition, their responses to periodontal basic treatment were different (P < 0.05). After treatment, the improvement of CAL and decline in BOP were more obvious in the elder sister,and the proportion of different periodontal pocket depths in the elder sister decreased after treatment, while the de⁃ crease was slighter in the younger sister. Genetic tests revealed that the twins had the same genotypes at target suscepti⁃ bility genes (IL⁃1β⁃511, IL⁃1β+3953, TNF⁃α⁃308, FcγR⁃IIIb, VDR, and ER) and differential exon gene components, and that the suspected differential genes, e.g. ZFPM1, PTH2, ZFYVE16, and LY6G6C, might be related to their pheno⁃ typic differences.@* Conclusion@#These monozygotic twins had different phenotypes of generalized aggressive periodonti⁃ tis. Their shared susceptibility genes increased the risk of disease, and their different genetic mutations affected the phe⁃ notype of the disease

Differential expression analysis of schizophrenia susceptibility genes in single cells of human and mouse brain / 上海交通大学学报（医学版）

Objective: To investigate the expression patterns of schizophrenia susceptibility genes in different neuronal cell types of human and mouse brains. Methods: Schizophrenia susceptibility genes were studied based on four genetic study methods, including genome-wide association study, linkage and association study, copy number variation study and convergent functional genomics study. Single cell RNA-seq data of human and mouse brains were used to explore the expression patterns of schizophrenia susceptibility genes in specific cell types of neurons, astrocytes, microglia, oligodendrocytes, oligodendrocyte progenitor cells. Furthermore, the functions of schizophrenia risk genes identified only in human brains were analyzed by functional annotation tools from the DAVID database. Results: Comparisons were made about single cell RNA-seq data between human and mouse brains, and there existed distinct expression patterns of schizophrenia susceptibility genes across species. Neurons, astrocytes and oligodendrocytes from both human and mouse were shown to have more co-expressed schizophrenia susceptibility genes, while co-expression of schizophrenia susceptibility genes in microglia and oligodendrocyte progenitor cells rarely existed. In addition, schizophrenia risk genes expressed only in human were involved in the regulation of neural synaptic plasticity and calcium signaling pathway. Conclusion: The schizophrenia susceptibility genes have distinct expression profiles at the single cell level in human and mouse brains, which provides clues and evidence for revealing the etiological mechanism of schizophrenia based on mouse model research.

Advances in the study of susceptibility genes to bronchial asthma in children Table 1 Genome-wide association study found some new bronchial asthma and related phenotype genes in recent years / 中华实用儿科临床杂志

Bronchial asthma(asthma for short)is a complex heterogeneous disease,which is caused by multi-ple gene-environmental interaction. With the progress of asthma gene research,some new childhood asthma suscepti-bility genes have been found,and the influence of genes interaction with environment on asthma is being widely atten-ded;different genetic loci combination can predict the onset of childhood asthma. Now,the history of asthma gene re-search and some newly discovered childhood asthma susceptibility genes in recent years and different genetic loci com-bination prediction effect and so on were introduced.

Association between Polymorphism of the BRCA2 Gene rs206115 Loci and Sporadic Breast Cancer / 中国医科大学学报

Objective To analyze the correlation between polymorphism of the BRCA2 gene rs206115 loci and sporadic breast cancer in Inner Mongolia. Methods We enrolled patients from the Affiliated Hospital of Inner Mongolia Medical University from December 2015 to December 2016 who underwent breast surgery and were confirmed by pathology, resulting in a total of 101 cases of primary sporadic breast cancer (case group) and benign breast diseases (control group). DNA was extracted from blood samples and analyzed using polymerase chain reaction (PCR) and direct sequencing methods for determining the BRCA2 gene rs206115 loci polymorphism. SPSS 17.0 was used for statistical analysis. Results In this experiment, regardless of whether the patients were Han or Mongolian, the rs206115 loci could be detected in 3 kinds of genotypes:AA, AG, and GG. The BRCA2 gene rs206115 locus gene polymorphism was not significantly different between the case and control groups (χ2=3.490, P = 0.175). The A allele frequency of the BRCA2 gene rs206115 loci in the case group was significantly increased compared to the control group (χ2=4.259, P = 0.039). Conclusion The A allele of rs206115 may be one of the susceptibility alleles in sporadic breast cancer in Mongolian and Han populations.

Expression of BRCA1 in sporadic invasive breast cancer and its significance / 医学研究生学报

Objective　BRCA1 is one of the most important susceptibility genes of breast cancer. The article aimed to investigate the expression of BRCA1 and its correlation in sporadic invasive breast cancer.　Methods　The expressions of BRCA1, ER, PR, HER2 and Ki67 in 618 cases of sporadic invasive breast cancer in our hospital from January 2015 to December 2017 were detected with immunohistochemistry in order to investigate and analyze the expression of BRCA1 and its correlation with molecular classification, histological type and other related molecular markers in sporadic invasive breast cancer.　Results　The positive rate of BRCA1 was 44.2% consisting of 30.3% weak positive(+) and 13.9% strong positive(++). The positive rates of ER, PR, and HER2 are 60.8%, 54.7%,and 24.9%. The proliferation index ≤30% of Ki67 was 70.7%, >30% was 29.3%. The expression of BRCA1 in luminal type A was significantly lower than the other four types of sporadic invasive breast cancer(P<0.05). The expression of BRCA1 in breast cancer with medullary histological features was significantly lower than those of the other types of breast cancer(P<0.05). There was significant difference between the expression of BRCA1 and the expressions of ER, HER2 and Ki67 (P<0.01). The expression of BRCA1 had positive correlation with expression of HER2 in sporadic invasive breast cancer (r=0.117,P<0.01).　Conclusion　The expression of BRCA1 in sporadic invasive breast cancer with triple negative subtype and medullary histological features is down-regulated and BRCA1 may affect the development and progression of sporadic invasive breast cancer.

Genetic progress of childhood absence epilepsy / 上海交通大学学报（医学版）

Childhood absence epilepsy (CAE) is an important kind of epileptic syndrome of genetic generalized epilepsies (GGEs) with prevalence of 5.8/100 000-7.1/100 000. The genetic mechanism of CAE is always the hotspot of research. Susceptibility genes including calcium channel and γ-aminobutyric acid receptor as well as copy number variations (CNVs) have been found. However, those mechanisms cannot explain all the situations since the genetic content of CAE is rather complicated. Nowadays, with new susceptibility genes and genetic mechanisms coming to light, researchers are supposed to study this problem from the point of associated epileptic syndromes. In this review, the genetic features, probable mechanisms of CAE and therapeutic drugs were summarized.

Molecular genetics of juvenile idiopathic arthritis and clinical significance / 中华实用儿科临床杂志

Juvenile idiopathic arthritis (JIA) is the most common disease in chronic rheumatic disorders,and also the major disability-causing disease in childhood.It is known that genetics may play a definite role in the pathogenesis of JIA.With the application of molecular genetics technology to JIA study,a panel of JIA-susceptible or-related genes have been revealed,among of which human leukocyte antigen loci demonstrate the highest risk correlation.JIA genetics also presents heterogenicity to some extent as with clinical heterogenicity,some of which have demonstrated certain clinical significance in evaluation of the outcome of JIA.However,more noteworthily,the current knowledge on JIA genetics may provide useful clue to future research of JIA.The review focuses on current progression and future issues in the study of JIA genetics,and thereby helps understand the pathogenesis of JIA and predict the clinical outcome.

Genetic progress of childhood absence epilepsy / 上海交通大学学报（医学版）

Childhood absence epilepsy (CAE) is an important kind of epileptic syndrome of genetic generalized epilepsies (GGEs) with prevalence of 5.8/100 000-7.1/100 000.The genetic mechanism of CAE is always the hotspot of research.Susceptibility genes including calcium channel and γ-aminobutyric acid receptor as well as copy number variations (CNVs) have been found.However,those mechanisms cannot explain all the situations since the genetic content of CAE is rather complicated.Nowadays,with new susceptibility genes and genetic mechanisms coming to light,researchers are supposed to study this problem from the point of associated epileptic syndromes.In this review,the genetic features,probable mechanisms of CAE and therapeutic drugs were summarized.

Correlation of 41 loci of single nucleotide polymorphisms with testicular germ cell tumor / 中华男科学杂志

<p><b>Objective</b>To identify genetic susceptibility genes and the loci of their single nucleotide polymorphisms (SNPs) in patients with testicular germ cell tumor (TGCT) and provide some new ideas for the prediction, diagnosis and treatment of TGCT.</p><p><b>METHODS</b>We identified 41 SNP loci of TGCT-related genetic susceptibility genes from the literature published abroad. Using the iMLDRTM genotyping technique, we examined the SNP loci of the genetic susceptibility genes in the blood samples from 76 TGCT patients (aged 16－68 years) and 148 healthy men (aged 22－61 years) in China and analyzed their correlation with TGCT.</p><p><b>RESULTS</b>In China, TGCT was found to be correlated with the SNP loci rs2978381, rs10146204, rs12435857 and rs1256063 of the ESR2 gene, rs9397080 of the ESR1 gene, rs11202586 of the PTEN gene, rs2606345 and rs4646903 of the CYP1A1 gene, and rs1456432 of the CYP19A1 gene.</p><p><b>CONCLUSIONS</b>The results of our study indicated some difference in the positive SNP loci of the TGCT patients between Chinese and foreign cohorts as well as in different groups in China.</p>