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At least 253 records · Page 14Linked to original sources
PubMed2006

[Relationship between genetic polymorphism in hMTH1c.83, hOGG1c.326 and hMYHc.335 and risks of chronic benzene poisoning].

OBJECTIVE: To explore the relationship between genetic polymorphisms in hMTH1, hOGG1 and hMYH and risks of chronic benzene poisoning (CBP). METHODS: A case control study was conducted. One hundred and fifty-two BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. The polymerase chain reaction restrained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) on c.83 of hMTH1 gene, c.326 of hOGG1 gene and c.335 of hMYH gene. RESULTS: There were 2.51 times (OR(adj) = 2.51, 95% CI: 1.14-5.49, P = 0.02) and 2.49 times (OR(adj) = 2.49, 95% CI: 1.52-4.07, P < 0.01) risks of BP for individuals carrying genotypes of hMTH1c.83Val/Met + Met/Met or hOGG1c.326Cys/Cys compared with individuals carrying genotypes of hMTH1c.83Val/Val or hOGG1c.326Ser/Cys + Ser/Ser, respectively. Compared with individuals carrying genotypes of hOGG1c.326Cys/Cy and hMYHc.335 is/His at the same time, there was 0.33 times (OR(adj) = 0.33, 95% CI = 0.15-0.72, P = 0.01) risks of BP for these with genotypes of hOGG1c.326Ser/Cys + Ser/Ser and hMYHc.335His/Gln + Gln/Gln simultaneously. In the smoking group, there was 0.15 times (OR(adj) = 0.15, 95% CI: 0.03-0.68, P = 0.01) risks of BP for subjects carrying genotypes of hMYHc.335His/Gln + Gln/Gln compared with these carrying genotypes of hMYHc.335His/His. CONCLUSION: Polymorphisms of hMTH1 Val83 Met and hOGG1 Ser326Cys may contribute to altered risks of CBP, and potential interaction may exist among polymorphisms of hOGG1 Ser326Cys and hMYH His335Gln.

Adult↗
PubMed1999

Update: genetic polymorphism of drug metabolizing enzymes in humans.

The cytochrome P450 (P450 or CYP) monooxygenases, CYP2D6, CYP2C19, CYP2E1 and CYP2C9, and non-P450 monooxygenases, N-acetyltransferase, thioprine methyltransferases and dihydropyrimidine dehydrogenase, all display polymorphism. CYP2D6 and CYP2C19 have been studied extensively and, despite their low abundance in the liver, they have been found to catalyse the metabolism of many drugs. CYP2D6 has many allelic variants, whereas CYP2C19 has only two. Most variants are translated into inactive, truncated proteins or fail to express protein. There is, as yet, no clear information about CYP2E1 polymorphism. In addition, genetic differences in certain foreign-compound metabolizing enzymes, such as Phase II enzymes, have been shown to be associated with an increased risk of developing environmentally and occupationally related diseases such as cancer. When two drugs that are substrates of a polymorphic CYP enzyme are administered concomitantly during drug therapy, each will compete for that enzyme and competitively inhibit the metabolism of the other substrate. This can result in toxicity. Patients who are poor metabolizers (PMs), extensive metabolizers (EMs) and ultrarapid metabolizers (URMs) can be identified. Having such information will help in determining the appropriate dosage of certain drugs when treating patients with an inherited abnormality of a drug-metabolizing enzyme. In view of the remarkable progress in this particular field, it is to be expected that more genetic polymorphisms will be discovered in the near future.

Cytochrome P-450 Enzyme System↗
PubMed1996

Cytochrome P450: genetic polymorphism and drug interactions.

In this review, after a short discussion of our knowledge about cytochrome P450 isoenzymes, two important sources of variability in the metabolism of drugs by cytochrome P450 are described, i.e. genetic factors and drug-drug interactions. Many hepatic cytochrome P450 enzymes play an important role in the oxidative biotransformation of numerous drugs and other foreign compounds, and of many endogenous substrates. In humans more than 20 different isoenzymes of cytochrome P450 responsible for the hepatic metabolism of drugs, have been identified. They are classified into families and subfamilies on the basis of the degree of amino acid similarity. Cytochrome P450 isoenzymes are regulated by both genetic and environmental factors. Of particular interest is genetic polymorphism in drug oxidation. Two genetic polymorphisms in drug oxidation are well known, the sparteine/debrisoquine (CYP2D6) polymorphism and the mephenytoin oxidation (CYP2C19) polymorphism. As a result of these polymorphisms, two phenotypes exist in the population, poor and extensive metabolizers. Poor metabolizers may be prone to adverse reactions towards drugs with a narrow therapeutic range. In extensive metabolizers clinically significant drug interactions between drugs metabolized by the same isoenzyme can occur.

Biotransformation↗
PubMed2006

[Relationship between genetic polymorphism of interleukin-6 and pneumoconiosis].

OBJECTIVE: To explore the relationship between interleukin-6 (IL-6) (-634C/G) genetic polymorphisms and the pneumoconiosis. METHODS: A total of 104 male stage I pneumoconiosis patients diagnosed by the Pneumoconiosis Diagnosis Expert Panel according to the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ 70 - 2002) were selected. The pneumoconiosis comprised 66 silicosis and 38 coal worker' pneumoconiosis (CWP). A total of 122 workers exposed to same dusts as the patients but without pneumoconiosis including 77 exposed to silica dusts and 45 to coal dusts were selected. The patients and the controls had the same dust exposure history. The peripheral venous blood was drawn from each subject. The IL-6 (-634C/G) genetic polymorphisms were detected by polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP) techniques. RESULTS: The frequencies of IL-6 (-634C/G) (CC, CG and GG) genotypes were 66.7%, 19.7% and 13.6% in silicosis group, 42.9%, 42.9% and 14.2% in silica dust exposure group, 73.7%, 18.4% and 7.9% in CWP group, 51.1%, 35.6% and 13.3% in coal dust exposure group respectively. The statistical analysis indicated that there was significant difference in the frequencies of IL-6 (-634C/G) (CC, CG and GG) genotypes between silicosis patients and workers exposed to silica dusts (P < 0.05). CONCLUSION: IL-6 (-634 C/G) genetic polymorphisms might play a role in the occurrence of silicosis.

Adult↗
PubMed2003

Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentrations.

This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8-hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a significant correlation with the 1-OHP concentration in all subjects (p<.001) and in smokers (p<.01), and with the 2-naphthol level in non-smokers (p<.01). The 8-OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8-OHdG and 1-OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The urinary 2-naphthol level significantly correlated with the 8-OHdG level only in subjects with the GSTM1 null-type. In conclusion, there is a significant correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Genetic polymorphisms of MnSOD, GSTM1, GSTT1, and OGG1 in coal workers' pneumoconiosis.

Little is known about the genetic susceptibility to coal workers' pneumoconiosis (CWP). We investigated the association between genetic polymorphisms of MnSOD, GSTM1, GSTT1, or OGG1 and susceptibility to CWP. The study population was composed of 259 Chinese retired coal miners who had similar dust exposure histories. Of these, there were 99 cases with International Labor Organization chest radiologic criteria for CWP and 160 controls (with no radiologic criteria for CWP). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Polymerase chain reaction-based techniques evaluated the genotypes of all study subjects. There were no differences in genotype frequency of MnSOD, GSTM1, GSTT1, and OGG1 between miners with CWP and miners without CWP, by logistic regression analysis. Cumulative dust exposures, but not genetic polymorphisms, were associated significantly with the presence of CWP. This study illustrates the complexity of factors that may contribute to the development of CWP.

Aged↗
PubMed2005

Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women.

To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant (P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD (P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype (P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women.

Adult↗
PubMed1991

Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene.

We identified genetic polymorphisms in the 5'-flanking region of the human cytochrome P450IIE1 gene and investigated the effect of these polymorphisms on the transcriptional regulation of the gene. PCR direct sequencing of the two homozygous alleles [types A (c1/c1) and C (c2/c2)] revealed the existence of several point mutations in the distal 5'-flanking region of the gene, but no differences in the proximal promoter region. The DNA segment (-1372 to -960) placed upstream of SV40 promoter and the chloramphenicol acetyltransferase (CAT) gene enhanced the expression of the gene, and the enhancement of expression by type C DNA was about 10 times that by its type A counterpart. DNase I footprinting analysis showed at least one protected region in which one of the polymorphic loci (RsaI polymorphism) was located. The DNase I sensitivities and protection profiles of the two genotypes were different. The protected region had high homology to the consensus sequence of the binding region of liver specific transcription factor HNF1 (LF-B1), and this was confirmed by gel retardation assay. These results indicate that genetic polymorphisms in the 5'-flanking region of the human P450IIE1 gene affect its binding of trans-acting factor and change its transcriptional regulation. This may lead to inter-individual differences of microsomal drug oxidation activity.

Amino Acid Sequence↗
PubMed1990

The genetic polymorphism of debrisoquine/sparteine metabolism-molecular mechanisms.

The genetic polymorphism of debrisoquine/sparteine metabolism is one of the best studied examples of a genetic variability in drug response. 5-10% of individuals in Caucasian populations are 'poor metabolizers' of debrisoquine, sparteine and over 20 other drugs. The discovery and the inheritance of deficient debrisoquine/sparteine metabolism are briefly described, followed by a detailed account of the studies leading to the characterization of the deficient reaction and the purification of cytochrome P-450IID1, the target enzyme of this polymorphism. It is demonstrated by immunological methods that deficient debrisoquine hydroxylation is due to the absence of P-450IID1 protein in the livers of poor metabolizers. The cloning and sequencing of the P-450IID1 cDNA and of IID1 related genes are summarized. The P-450IID1 cDNA has subsequently led to the discovery of aberrant splicing of P-450IID1 pre-mRNA as the cause of absent P-450IID1 protein. Finally, the identification of mutant alleles of the P-450IID1 gene (CYP 2D) by restriction fragment length polymorphisms in lymphocyte DNA of poor metabolizers is presented.

Debrisoquin↗
PubMedDate not supplied

[The genetic polymorphism of the grape studied by RAPD analysis].

Genetic polymorphism in plant of 3 genera of Vitaceae family, 11 species of Vitis genera, 10 cultivars of Vitis vinifera and 4 cultivars that obtained from distant hybridization was studied. According to date of RAPD analysis genetic distances were determined and phylogenetic dendrogram was constructed. The possibility of using PCR for evaluation of breeding material by the levels of genetic relations was shown.

Base Sequence↗
PubMed2000

Genetic polymorphisms in head and neck cancer risk.

OBJECTIVE: To assess whether genetic polymorphisms implicated as risk factors for other tobacco-associated malignancies are associated with altered risk of head and neck squamous cell carcinoma. DESIGN: Case-control study. SUBJECTS: One hundred sixty patients with head and neck squamous cell carcinoma recruited from a university-based head and neck oncology clinic and 149 population-based controls. METHODS: Genotyping of the CYP1A1 (Ile462Val), GSTM1 (null), GSTP1 (Ile105Val), GSTT1 (null), and P53 (Arg72Pro) genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. In addition, a questionnaire was used to collect demographic information from each subject. RESULTS: Cases were significantly older (p <.0001) and had significantly greater tobacco use (p <.0001) and were more likely to be male (p <.0001) than were control subjects, thus confirming known risk factors for this disease. When cases and controls were compared by simple chi-square analysis, only the frequency of CYP1A1 (Ile462Val) polymorphism was significantly different between cases and controls (OR =.42; 95% CI =.18-.99; p <.04). However, with a logistic regression model to control for known risk factors, we were unable to demonstrate a significant association with head and neck cancer for any of the polymorphisms tested, including CYP1A1. CONCLUSIONS: This population fails to identify a relationship between the above-mentioned polymorphisms and head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed1984

Genetic polymorphism of the seventh component of complement in a Japanese population.

Genetic polymorphism of C7 in a Japanese population has been described, using polyacrylamide gel isoelectric focusing electrophoresis followed by an electrophoretic blotting technique. Phenotypes of C7 were classified into six common patterns, and observed phenotypes were produced by autosomal codominant at a single locus with three alleles. Three common alleles, designated C7*B, C7*M and C7*A, were found, and gene frequencies calculated from 494 individuals showed C7*B = 0.858, C7*M = 0.096 and C7*A = 0.046, respectively. It is noteworthy that both C7*M and C7*A have polymorphic frequencies in the Japanese population. The distribution of phenotypes fitted the Hardy-Weinberg equilibrium. Results indicate that the electrophoretic blotting technique, which has high specificity and sensitivity, is applicable in the study of heterogeneity of protein antigens.

Adult↗
PubMed1994

Genetic polymorphisms of the CST2 locus coding for cystatin SA.

A new genetic polymorphism of cystatin SA has been identified in human submandibular-sublingual saliva by means of basic gel electrophoresis and immunoblotting with anti-cystatin S. Two proteins, SA1 and SA2, are given by two alleles of CST2, viz., CST2*1 and CST*2. Inheritance is controlled by two codominant alleles at an autosomal locus. This hypothesis is supported by studies of 16 families 32 children. Gene frequencies for CST2*1 and CST2*2 are 0.935 and 0.065, respectively (n = 341). Eighteen amino acids determined among 20 N-terminal residues of cystatin SA2 are identical with the sequence encoded by CST2. Three forms of cystatin S (mono-phosphorylated cystatin S, di-phosphorylated cystatin S, and non-phosphorylated cystatin S) are present in the 341 saliva samples tested.

Amino Acid Sequence↗
PubMed1989

[Genetic polymorphism of isoniazid acetylation in Chilean patients with tuberculosis].

We studied genetic polymorphism of isoniazid acetylation in 47 tuberculous patients treated with 4 drugs between Aug 1987 and Dec 1988. Inactivation of isoniazid was estimated from urine samples after administration of the drug (10 mg/kg). There were 18 slow and 29 fast acetylators. The frequency of the slow mutant gene was estimated at 0.612, which is intermediate between values found in american natives (0.46) and western europeans (0.73). No associations of the presence of slow gene with sex, ABO group, ancestors, socioeconomic level, undernutrition, alcoholism or tobacco consumption were found.

Acetylation↗
PubMed1991

Genetic polymorphisms in drug metabolism--its relevance to Asian populations.

Genetic polymorphisms in drug metabolism represent a significant although largely underrecognised problem in therapeutics. The presence of mutant alleles within a population may result in substantial interindividual and interethnic variability in the efficacy/toxicity ratios for many drugs. The practical difficulties involved in phenotyping both individuals and populations alike have hindered the generation of much useful information, especially those in relation to non-Caucasian populations. Newer techniques have provided clearer insights into the molecular genetics of these polymorphisms. It is hoped that these techniques will eventually lead to relatively non-invasive genotyping procedures that will allow the systematic characterisation of the diverse ethnic groups in Asia.

Aldehyde Dehydrogenase↗
PubMed2006

Genetic polymorphism of XRCC3 Thr241Met and breast cancer risk: case-control study in Korean women and meta-analysis of 12 studies.

To evaluate the relationship of genetic polymorphism in XRCC3 Thr(241)Met and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 1995-2001. Information on demographic characteristics and other information were collected by interviewed questionnaire. Genetic polymorphisms of XRCC3 Thr(241)Met (C > T) was determined by single base extention assay. The frequency of Thr/Thr, Thr/Met, and Met/Met genotype were 89.4, 10.4, 0.2% in cases and 92.3, 7.7, 0.0% in controls, respectively. Genotype distribution in controls fit well to the Hardy-Weinberg equilibrium (P = 0.74). XRCC3 codon 241 Thr/Met or Met/Met genotype moderately increased the risk of breast cancer (OR = 1.4, 95% CI: 0.87-2.33), but not significant in this study. In the results of meta-analysis using twelve reports, however, Thr/Met or Met/Met genotype increased the risk of breast cancer (OR = 1.08, 95%CI: 1.00-1.17). In conclusion, although the genetic polymorphism of XRCC3 Thr(241)Met was unlikely to have a substantial overall association in Korean women, the meta-analysis of studies, including ours, provided that Thr/Met and Met/Met was weakly increased the risk of breast cancer compare to Thr/Thr genotype.

Asian People↗
PubMed2006

[Relationship of genetic polymorphism in APE1 and ADPRT to risks of chronic benzene poisoning].

OBJECTIVE: To explore the relationship between genetic polymorphisms in apurinic/apyrimidinic endonuclease (APE1) and ADP ribosyltransferase (ADPRT) and individuals' susceptibility to chronic benzene poison ing (BP). METHODS: A case-control study was conducted. One hundred and fifty-two B P patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. The mismatched bases combined to create restriction site with restrained fragment length polymorphism technique (CRS-RFLP) was used for detecting the single nucleotide polymorphisms (SNPs) at Asp148Glu of APE1 gene and Val762Ala of ADPRT gene. RESULTS: There was no significant difference in the distribution of genotypes of APE1Asp148Glu and ADPRTVal762Ala between the patients and the control groups. Compared with individuals having genotype of APE1Asp148Glu T/T without habit of alcohol consumption, there was a 4.13 times increased risk of BP for the alcohol user with genotype of APE1Asp148Glu T/T (OR = 4.13, 95% CI: 1.07 - 15.85, P = 0.03). The analysis of Logistic regression showed that smoking may play some role in modifying the risk of cironic benzene poisoning (OR = 0.33, 95% CI: 0.14 - 0.75, P = 0.01). CONCLUSION: The genetic polymorphisms in APE1Asp148Glu, ADPRTVal762Ala are not related to the risk of BP. Potential interaction is found between alcohol consumption and polymorphism of APE1Asp148Glu. Further study is needed to elucidate this interaction.

ADP Ribose Transferases↗
PubMed2003

[The genetic polymorphism of 8 STR loci in northern Chinese Han and Uygur populations].

OBJECTIVE: The genetic polymorphism of 8 STR loci, was studied in northern Chinese Han and Uygur populations. METHODS: The 8STR loci(vWA,TH01, TP0X, CSF1P0, D5S818, D13S317, D7S820, D16S539) were analyzed and genotyped by fluorescent prime labeling kit and gene scan technology. RESULTS: 62 alleles were found in 100 individuals of Han population, CPE value was 0.9975; And 52 alleles were found in 50 individuals of Uygue population, CPE value was 0.9973. The TDP of both was beyond 0.9999. The difference of gene frequency between the two populations was significant. CONCLUSION: The genetic polymorphism of the 8 STR loci in the Han and Uygue populations is high, there are ethic differences in frequency distribution.

Alleles↗