OBJECTIVETo determine the correlation of the CYP1A1 (rs4646422) gene polymorphisms with male infertility in the Chinese Han population.

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.

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.

CONCLUSIONThe CYP1A1 (rs4646422) gene polymorphisms might not be correlated with male infertility in the Chinese Han population.

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

BACKGROUND AND OBJECTIVES: Human mesenchymal stem cells (hMSCs) are attractive candidates for cell therapy and regenerative medicine due to their multipotency and ready availability, but their application can be complicated by the factors such as age of the donors and senescence-associated growth arrest during culture conditions. The latter most likely reflects the fact that aging of hMSCs is associated with a rise in intracellular reactive oxygen species, loss of telomerase activity, decrease in human telomerase reverse transcriptase (hTERT) expression and finally eroded telomere ends. Over-expression of telomerase in hMSCs leads to telomere elongation and may help to maintain replicative life-span of these cells. The aim of this study was to evaluate of the effect of L-carnitine (LC) as an antioxidant on the telomerase gene expression and telomere length in aged adipose tissue-derived hMSCs. METHODS: For this purpose, cells were isolated from healthy aged volunteers and their viabilities were assessed by MTT assay. Quantitative gene expression of hTERT and absolute telomere length measurement were also performed by real- time PCR in the absence and presence of different doses of LC (0.1, 0.2 and 0.4 mM). RESULTS: The results indicated that LC could significantly increase the hTERT gene expression and telomere length, especially in dose of 0.2 mM of LC and in 48 h treatment for the aged adipose tissue-derived hMSCs samples. CONCLUSION: It seems that LC would be a good candidate to improve the lifespan of the aged adipose tissue-derived hMSCs due to over-expression of telomerase and lengthening of the telomeres.
Aging ; Carnitine* ; Cell- and Tissue-Based Therapy ; Cytochrome P-450 CYP1A1 ; Gene Expression* ; Humans* ; Mesenchymal Stromal Cells* ; Polymerase Chain Reaction ; Reactive Oxygen Species ; Regenerative Medicine ; Telomerase ; Telomere ; Tissue Donors ; Volunteers

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

OBJECTIVETo explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning (CBP) comprehensively by case-control design.

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.

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.

CONCLUSIONGene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.

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

OBJECTIVETo investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study.

METHODSA total of 457 Cantonese nuclear families,consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943), were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma.

RESULTSFBAT analysis showed that the minor allele frequencies (MAF) of the two SNP were 0.442 (C) and 0.339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification: chi2 = 2.399, P = 0.301; with stratification: low-titer group (VCA-IgA <1:80), MAF = 0.457 (C), chi2 = 1.221, P = 0.543; high-titer group (VCA-IgA > or = 1:80), MAF = 0.427 (C), chi2 =2.832, P = 0.243) . For m2 polymorphism, when VCA-IgA <1:80, the G allele showed decreased transmission under additive and dominant model (MAF = 0.347 (G); Zadditive = -2.120, Padditive = 0.034; Zdominant = - 2.303, Pdominant = 0.021) and a boundary P value was got with global statistic (chi2 = 5.394, P = 0.067) . Haplotype TG (0.057), constructed by m1 and m2, might decrease nasopharyngeal carcinoma risk (Z= -2.002, P=0.045). A boundary P value was also got with global statistic (chi2 =7.067, P=0.070).

CONCLUSIONThere was no statistical significance between m1 polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.

Cytochrome P-450 CYP1A1 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Nasopharyngeal Neoplasms ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo study the relationship between CYP1A1 genetic polymorphism and intrahepatic cholestasis of pregnancy (ICP) in Chengdu of China.

METHODSMspI and Ile/Val genotypes of CYP1A1 gene were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification-PCR (ASA-PCR) in a case-control study, including 100 cases of ICP and 100 controls.

RESULTSThere was no significant correlation between MspI polymorphism and ICP susceptibility (P>0.05). However, the Ile/Val+Val/Val genotypes of CYP1A1 significantly increased the risk of ICP (P=0.047, OR=1.768).

CONCLUSIONThe Ile/Val polymorphism in exon 7 of CYP1A1 may be associated with the susceptibility of ICP in Chengdu. The MspI polymorphism of CYP1A1 is not associated with the risk of ICP in Chengdu.

Case-Control Studies ; Cholestasis, Intrahepatic ; genetics ; Cytochrome P-450 CYP1A1 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications ; genetics

BACKGROUNDVariation in prostate cancer incidence between different racial groups has been well documented, for which genetic polymorphisms are hypothesized to be an explanation. We evaluated the association between polymorphisms in the cytochrome P-450 CYP1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes and genetic susceptibility to prostate cancer in Chinese men.

METHODSTwo hundred and eight prostate cancer patients and 230 age matched controls were enrolled in this study. All DNA samples from peripheral blood lymphocytes were genotyped for common genetic polymorphisms of the CYP1A1 and GSTM1 genes using the oligonucleotide microarray (DNA chip) technique and the polymorphism results confirmed by sequencing. The different polymorphisms in prostate cancer patients were also analyzed according to age at diagnosis, prostate specific antigen level, cancer stage and grade (Gleason score).

RESULTSThe prevalence of the GSTM1 (0/0) genotype was significantly higher in prostate cancer patients (58.2%) than in controls (41.7%, P<0.05). Further analysis demonstrated that the prostate cancer patients with a GSTM1 (0/0) genotype were younger than those with the GSTM1 (+/+) genotype (P=0.024). No significant differences in the frequency distributions of CYP1A1 polymorphisms were observed between prostate cancer patients and controls.

CONCLUSIONGSTM1 (0/0) gene polymorphism may be linked to prostate cancer risk and early age of onset in Chinese.

Aged ; Aged, 80 and over ; Cytochrome P-450 CYP1A1 ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Glutathione Transferase ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Prostatic Neoplasms ; genetics

PURPOSE: Oral cancer is the fifth most common form of cancer in the world and comprises 6.5% of all cancer deaths. Since one of the major risk factors for oral cancer is tobacco use, we hypothesized that polymorphic genes coding for tobacco carcinogen-metabolizing enzymes may play a role in oral cancer susceptibility. MATERIALS AND METHODS: To investigate the association between polymorphisms of the CYP1A1 and GSTM1 genes and risks for oral squamous cell carcinoma (OSCC) in the Korean population, the prevalence of the CYP1A1 Mspl and GSTM1 null polymorphisms were examined in 72 patients with histologically confirmed primary OSCC, as well as in 221 healthy control subjects. RESULTS: A significant risk increase for oral cancer was observed among subjects with the homozygous CYP1A1 (m2/m2) genotype (OR=3.8, 95% CI=1.9-7.7), but not the GSTM1 null genotype (OR=0.7, 95% CI=0.4-1.3). Risk for oral cancer was significantly increased in subjects with the homozygous CYP1A1 (m2/m2)genotype, regardless of smoking history (smokers; OR=4.4; 95% CI=1.2-16.3; non- smokers OR=4.9; 95% CI=1.9-12.5). Using the potentially most protective genotype GSTM1 (+)/CYP1A1 [(m1/m1)+ (m1/m2)]as the reference group, an increased risk for oral cancer was observed among subjects with the GSTM1 (+)/ CYP1A1 (m2/m2) (OR= 2.0, 95% CI=0.8-5.2), and GSTM1 (-)/ CYP1A1 (m2/m2) (OR=4.9, 95% CI=1.5-15.5) genotypes (p < 0.009, (chi-square trend test). CONCLUSION: Our results suggest that individuals with a genotype of CYP1A1 (m2/m2) and GSTM1(-) are highly susceptible for OSCC and that the CYP1A1 (m2/m2) genotype is closely associated with increased risk of OSCC in Koreans.
Smoking/epidemiology ; Risk Factors ; Mouth Neoplasms/epidemiology/*genetics ; Middle Aged ; Male ; Humans ; Homozygote ; Glutathione Transferase/*genetics ; Genotype ; *Genetic Predisposition to Disease ; Gene Deletion ; Female ; Cytochrome P-450 CYP1A1/*genetics ; Aged, 80 and over ; Aged ; Adult

OBJECTIVETo investigate the effects of the ethyl acetate extract of Semen Hoveniae (ESH) on liver microsomal cytochrome P450 isoenzyme in rats.

METHODThe rats were given orally the ESH in the doses of 0.14, 0.17, 0.2 g x kg (equivalent to the crude herb) for 10 days respectively. Rat liver microsomal cytochrome P450, NADPH-Cyt C reductase, erythromycin N-demethylase (ERD), Aniline hydroxylase (ANH), aminopyrine N-demethylase (ADM) activities were quantitated by UV chromatography. The levels of mRNA expression of CYP1A1, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcripatase-polymerase chain reaction (RT-PCR).

RESULTThe cytochrome P450 content, NADPH-Cyt C reductase activities and erythromycin N-demethylase (ERD) activities were not affected. Aniline hydroxylase (ANH) activities in liver were decreased by up to35.1%; aminopyrine N-demethylase (ADM) activitiesin liver were increased by up to 42.4%. The mRNA expression of CYP1A1, CYP2C11 and CYP3A1 were found to be increased markedly.

CONCLUSIONA specific effect of ESH on liver microsomal cytochrome P450 isoenzyme in rats was observed in this investigation. ESH had various effects on liver microsomal cytochrome P450 isoenzyme.

Acetates ; chemistry ; Aminopyrine N-Demethylase ; metabolism ; Aniline Hydroxylase ; genetics ; metabolism ; Animals ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP1A1 ; 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 ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Gene Expression Regulation, Enzymologic ; drug effects ; Male ; Microsomes, Liver ; drug effects ; enzymology ; NADPH-Ferrihemoprotein Reductase ; genetics ; metabolism ; Plants, Medicinal ; chemistry ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Rhamnaceae ; chemistry ; Seeds ; chemistry ; Steroid 16-alpha-Hydroxylase ; genetics ; metabolism