Approximately 2,300 genes are found to be associated with spermiogenesis and their expressions play important roles in the regulation of spermiogenesis. In recent years, more and more attention has been focused on the studies of the genes associated with oligospermia, asthenospermia and teratospermia and their molecular mechanisms. Some genes, such as GSTM1, DNMT3L, and CYP1A1, have been shown to be potentially associated with oligospermia; some, such as CATSPER1, CRISP2, SEPT4, TCTE3, TEKT4, and DNAH1, with asthenospermia; and still others, such as DPY19L2 and AURKC, with teratospermia. These findings have provided a molecular basis for the studies of the pathogenesis of oligospermia, asthenospermia and teratospermia, as well as a new approach to the exploration of new diagnostic and therapeutic techniques.
Asthenozoospermia ; genetics ; Aurora Kinase C ; genetics ; Calcium Channels ; genetics ; Cytochrome P-450 CYP1A1 ; genetics ; Cytoplasmic Dyneins ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Dyneins ; genetics ; Glutathione Transferase ; genetics ; Glycoproteins ; genetics ; Humans ; Male ; Membrane Proteins ; genetics ; Microtubule Proteins ; genetics ; Oligospermia ; genetics ; Spermatogenesis ; genetics ; Teratozoospermia ; genetics

<p>OBJECTIVETo determine the correlation of the CYP1A1 (rs4646422) gene polymorphisms with male infertility in the Chinese Han population.p><p>METHODSUsing the Mass ARRAY iPLEX GOLD technique, we conducted a case-control study on theCYPlA1 (rs4646422) gene polymorphisms in 636 infertile males aged 21-49 years (case group) and 442 normal healthy men aged 23-47 years (control group) of the Chinese Han population. We analyzed the genotypes and allele frequencies in the two groups ofsubjects with the SPSS 20.0 software.p><p>RESULTSCompared with the wild homozygous genotype GG, the heterozygous genotype AG (OR = 1.06, 95% CI 0.81-1.38) and homozygous genotype AA (OR = 1.11, 95% CI 0.56-2.21) showed no correlation with male infertility, nor did the mutant allele A (OR = 1.06, 95% CI 0.85-1.32) in comparison with the wild allele G.p><p>CONCLUSIONThe CYP1A1 (rs4646422) gene polymorphisms might not be correlated with male infertility in the Chinese Han population.p>
Adult ; Alleles ; Case-Control Studies ; China ; Cytochrome P-450 CYP1A1 ; genetics ; Gene Frequency ; Genotype ; Homozygote ; Humans ; Infertility, Male ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Young Adult

Dioscin has a wide range of biological effects and broad application prospects. However the studies concerning the toxicology and mechanism of dioscin is small. This article is to study the hepatotoxicity of dioscin and the effect of dioscin treatment on expression of aryl hydrocarbon receptor (AhR) mRNA and CYP1A mRNA and protein in HepG2 cells in vitro. Dioscin 0.5-32 µmol · L(-1) exposed to HepG2 cells for 12 h, cell viability was examined by CCK-8 assay and the release rate of lactate dehydrogenase (LDH) was to evaluate cell membrane damage. HepG2 cells morphologic changes were quantified by inverted Microscope, and the effect on production of reactive oxygen species (ROS) was detected by flow cytometry. The mRNA expression of CYP1A and AhR was evaluated by RT-RCR. The protein expression of CYP1A1 was detected by western blot. The cell viability was significantly inhibited after HepG2 cells were exposed to dioscin 0.5-32 µmol · L(-1). Compared with the control, the LDH release rate and ROS were significantly increased. The expression of CYPlA and AhR mRNA was increased. The expression of CYP1Al protein was increased after dioscin treatment, and resveratrol, an AhR antagonist, could downregulate the expression of CYP1A1. It follows that large doses dioscin has potential hepatotoxicity. The possible mechanism may be dioscin can active aryl hydrocarbon receptor (AhR) and induce the expression of CYP1A.
Cell Survival ; drug effects ; Chemical and Drug Induced Liver Injury ; etiology ; Cytochrome P-450 CYP1A1 ; genetics ; Diosgenin ; analogs & derivatives ; toxicity ; Hep G2 Cells ; Humans ; L-Lactate Dehydrogenase ; secretion ; RNA, Messenger ; analysis ; Reactive Oxygen Species ; metabolism ; Receptors, Aryl Hydrocarbon ; genetics

<p>OBJECTIVETo explore the association between CYP1A1*2A polymorphism and susceptibility to childhood acute lymphoblastic leukemia (ALL) through a Meta analysis.p><p>METHODSInclusion and exclusion criteria were formulated and English and Chinese databases (PubMed, OVID Database, CBM, CNKI, and Wanfang Data) were searched comprehensively. The studies (from January 1999 to April 2015) related to the association between CYP1A1*2A polymorphism and susceptibility to childhood ALL were collected. STATA 12.0 Software was applied to perform the Meta analysis for the articles included.p><p>RESULTSA total of 12 articles were included for analysis (11 English articles and 1 Chinese article), which involved 3 355 cases in total. The results of the Meta analysis showed a significant association between CYP1A1*2A polymorphism and susceptibility to childhood ALL (allele model: OR=1.31, 95% CI: 1.07-1.61; dominant model: OR=1.33, 95% CI: 1.13-1.56; codominant model: OR=1.30, 95% CI: 1.10-1.54). According to the results of a subgroup analysis based on ethnic origin, an increased risk of childhood ALL was observed in both Asian subgroup (dominant model: OR=1.57, 95% CI: 1.19-2.08; codominant model: OR=1.61, 95% CI: 1.20-2.17) and the Caucasian subgroup (allele model: OR=1.31, 95% CI: 1.04-1.63; dominant model: OR=1.22, 95% CI: 1.00-1.49).p><p>CONCLUSIONSCYP1A1*2A polymorphism may be associated with the genetic susceptibility to childhood ALL.p>
Cytochrome P-450 CYP1A1 ; genetics ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Genetic ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics

Cytochrome P-450 CYP1A1 ; genetics ; Genetic Predisposition to Disease ; Humans ; Logistic Models ; Pulmonary Disease, Chronic Obstructive ; complications ; Risk Factors ; Smoking ; adverse effects ; Venous Thromboembolism ; etiology ; genetics

<p>OBJECTIVETo investigate the effect of CYP1A1 and GSTM1 genetic polymorphisms and BPDE-DNA adducts on lung tumorigenesis.p><p>METHODSThe case control study has included 200 cases of lung cancer and 200 controls. DNA was extracted from blood samples of all subjects. The genotype of both CYP1A1 and GSTM1 were detected with PCR-based restriction fragment length polymorphisms (PCR-RELP). BPDE-DNA adducts were detected with competitive ELISA.p><p>RESULTSCYP1A1 mutant genotype and GSTM1 null genotype with smoke has increased the risk of lung cancer, with OR being 2.406(1.321-4.382), 2.755(1.470-5.163), respectively. The level of BPDE-DNA adducts in patients was greater than control, and the adduct level in ever smokers was higher than never smokers, the difference was statistically significant (P= 0.0252). GSTM1 null genotype individuals with BPDE-DNA level higher than 5 adducts/10(8) nucleotide have increased risk of lung cancer (OR= 1.988, 95%CI: 1.011-3.912). Compared with never smokers with CYP1A1 wild genotype, smokers with CYP1A1 mutation genotype had an increased risk of forming a higher level of DNA adducts (P= 0.0459). Smokers with GSTM1 null genotype formed more DNA adducts compared with never smokers with GSTM1 functional genotype (OR = 2.432, 95% CI: 1.072-4.517).p><p>CONCLUSIONGSTM1 null genotype with higher level DNA adducts may increase the risk of lung cancer. DNA adducts form easier in smokers with CYP1A1 mutation genotype and GSTM1 null genotype, which in turn may influence lung tumorigenesis.p>
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide ; Carcinogens ; Case-Control Studies ; Cytochrome P-450 CYP1A1 ; genetics ; DNA Adducts ; genetics ; Female ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Lung Neoplasms ; chemically induced ; enzymology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic

OBJECTIVE: To compare the difference in gene expression profiles between parental cell line and drug resistant cell line (CNE-1 and CNE-1/taxol) pre-treated or treated by drugs, and search for genes related to taxol resistance and reversal of taxol resistance phenotype. METHODS: cDNA microarray was used to detect the difference in gene expression profiles between 6 groups of cells. Combination of multiple filtering genes and detailed analysis of documented resistance genes were used to analyze the data. RESULTS: Through multiple filtering, 297 differentially expressed genes were screened. The expression of 17 genes was increased or decreased more than 5 folds in CNE-1/taxol compared with CNE-1.Through analyzing documented drug-resistant genes, MDR1 expression was not detected in each group. CYP1A1, one of P450 family members, was not expressed in CNE-1, but significantly increased expressions was found in CNE-1/taxol and these increased expressions were restored by cisplatin. The expression level of some members of tumor necrosis factor family was decreased in CNE-1/taxol and restored by cisplatin, including TNFAIP1, 3 and TNFRSF12A, 21. The differentially expressed members in the caspase family were caspase-4 and caspase-6. The expression of β-tubulin II was down-regulated in CNE-1/taxol. TSP1 was obviously down-regulated in CNE- 1/taxol compared with CNE-1, and a more significant down-regulation of TSP1 was found when treated by taxol. However, it was greatly up-regulated after cisplatin treatment in CNE-1/taxol. CONCLUSION Some genes are probably related to taxol resistance and reversal of taxol resistance in NPC cells: 297 differentially expressed genes detected by multiple filing, CYP1A1, some members of TNF family and another 17 genes whose differential expression is more than 5 folds between parental cell line and drug resistant cell line. Combination of multiple filtering genes and detailed analysis of documented resistance genes is a good method to study drug resistance and reversal of drug resistance in carcinoma cells.
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Cell Line, Tumor ; Cytochrome P-450 CYP1A1 ; genetics ; Drug Resistance, Neoplasm ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Nasopharyngeal Neoplasms ; pathology ; Oligonucleotide Array Sequence Analysis ; Paclitaxel ; pharmacology ; Proteins ; genetics ; Receptors, Tumor Necrosis Factor ; genetics ; TWEAK Receptor

Abstract: The activities of four CYP450 enzymes (CYP3A, 1A2, 2El and 2C) and the mRNA expression levels of CYP1A2, 2El, 2Cll and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg.kg-1 per day) and the high dose of BR combined with glycyrrhetinic acid (GA, 25 mg.kg-1 per day) or liquiritin (LQ, 20 mg.kg-1 per day) for 7 consecutive days. Compared with the control, brucine caused 24.5% and 34.6% decrease of CYP3A-associated testosterone 6beta-hydroxylation (6betaTesto-OH) and CYP2C-associated tolbutamide hydroxylation (Tol-OH), respectively, and 146.1% increase of CYP2El-associated para-nitrophenol hydroxylation (PNP-OH) at the high dose level. On the other hand, (BR+GA) caused 51.4% and 33.5% decrease, respectively, of CYP2El-associated PNP-OH and CYP1A2-associated ethoxyresorufin-O-de-ethylation (EROD) as compared with the high dose of BR group. Meanwhile, (BR+LQ) caused 41.1% decrease of CYP2El-associated PNP-OH and 37.7% increase of CYP2C-associated Tol-OH. The results indicated that the co-administration of BR with GA or LQ had effect on mRNA expression and activities of the CYP450 enzymes mentioned above to some extent, and the in vivo antagonism of LQ on BR-induced CYPs adverse effects and the in vivo inhibitory action of GA on CYP2E1 and 1A2 might play an important role in the detoxification of Radix Glycyrrhizae against Strychnos nux-vomica L.
Animals ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP1A1 ; metabolism ; Cytochrome P-450 CYP1A2 ; genetics ; metabolism ; Cytochrome P-450 CYP2E1 ; genetics ; metabolism ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Cytochrome P450 Family 2 ; Flavanones ; pharmacology ; Gene Expression Regulation, Enzymologic ; Glucosides ; pharmacology ; Glycyrrhetinic Acid ; pharmacology ; Hydroxylation ; Liver ; enzymology ; metabolism ; Male ; Nitrophenols ; metabolism ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Steroid 16-alpha-Hydroxylase ; genetics ; metabolism ; Steroid Hydroxylases ; metabolism ; Strychnine ; analogs & derivatives ; isolation & purification ; pharmacology ; Strychnos nux-vomica ; chemistry ; Tolbutamide ; metabolism

<p>OBJECTIVETo investigate the relationship between cytochrome P4501A1 (CYP1A1) Msp I gene polymorphism and childhood acute leukemia (AL).p><p>METHODSRelevant literature was extensively searched and screened by Pubmed and Wanfang Database, Chinese Science Journal Database and Chinese Journal Net. Various data consolidation, combined OR values and their 95% CI were tested by RevMan 4.2; Funnel plots were used for the bias analysis.p><p>RESULTSSix related literatures were found to meet the requirements. According to heterogeneity results, there was no significant difference in homozygous types(P>0.05), while there was significant difference in two others types (P all<0.05). For wild CYP1A1MspI homozygous for the reference group, Combined OR of heterozygous mutation, homozygous, heterozygous + homozygous mutation in AL and control groups were 1.18, 0.96, and 1.10 respectively. Subgroup analysis: Z values of CYP1A1MspI homozygous, heterozygous + homozygous in the acute lymphoblastic leukemia (ALL) and the control group were 0.10 and 0.76 respectively, Z values in non-acute lymphoblastic leukemia and control group were 0.74 and 0.75.p><p>CONCLUSIONThere is no correlation between CYP1A1MspI gene polymorphism and the susceptibility of childhood AL.p>
Acute Disease ; Child ; Cytochrome P-450 CYP1A1 ; genetics ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Leukemia ; enzymology ; genetics ; Polymorphism, Genetic

<p>OBJECTIVETo explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning (CBP) comprehensively by case-control design.p><p>METHODS152 CBP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. 30 single nucleotide polymorphisms (SNPs) in 13 genes such as CYP2E1 were tested by PCR-RFLP, sequencing approaches. Logistic regression model was used to detect main effects and 2-order interaction effects of gene and/or environment. Multifactor dimensionality reduction (MDR) was used to detect high-order gene-gene or gene-environment interactions.p><p>RESULTSBased on logistic regression, the main effects of GSTP1 rs947894, EPHX1 rs1051740, CYP1A1 rs4646903, CYP2D6 rs1065852 and rs1135840 were found to be significant (P < 0.05) while the confounding factors of sex, cigarette smoking, alcohol consumption and the intensity of benzene exposure were controlled. EPHX1 rs1051740 might be associated with CBP (P = 0.06). There existed 3 types of interactions were as followed: interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1 rs3813867 with EPHX1 rs3738047, EPHX1 rs3738047 with alcohol consumption(P < 0.05), while the main effects of CYP2E1 rs3813867 and EPHX1 rs3738047 were not significant (P > 0.05). The other SNPs did not show any significant associations with CBP. According to MDR, a 3-order interaction with the strongest combined effect was found, i.e. the 3-factor combination of CYP1A1 rs4646903, CYP2D6 rs1065852 and CYP2D6 rs1135840.p><p>CONCLUSIONGene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.p>
Adult ; Benzene ; poisoning ; Case-Control Studies ; Cytochrome P-450 CYP1A1 ; genetics ; Cytochrome P-450 CYP2D6 ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; Epoxide Hydrolases ; genetics ; Female ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Multifactor Dimensionality Reduction ; Occupational Exposure ; Polymorphism, Single Nucleotide ; Young Adult