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At least 1,099 records · Page 61Linked to original sources
PubMed2003

Association analysis for dopamine D3 receptor, dopamine D4 receptor and dopamine transporter genetic polymorphisms and P300 event-related potentials for normal young females.

OBJECTIVE: It has been demonstrated that the P300 components, a positive event-related potential, are heritable and are influenced by dopaminergic activity. We tested the genetic effects of the dopaminergic system in P300 components by association study. METHODS: In a sample population consisting of 120 normal young Han-Chinese females, we explored the association between the P300 components, and, the genetic polymorphisms including the dopamine D3 receptor (serine-to-glycine polymorphism in exon I), the dopamine D4 receptor (variable number tandem repeat polymorphism in exon III), and the dopamine transporter (variable number tandem repeat polymorphism in promoter region). RESULTS: No associations were demonstrated between the polymorphisms of these three genes and the P300 components. CONCLUSIONS: Our negative findings suggest that these genetic polymorphisms do not play a major role in the modulation of P300 event-related potentials.

Adult↗
PubMed2002

Serotonin transporter genetic polymorphisms and harm avoidance in the Chinese.

The association for the harm avoidance (HA) dimension, as assessed by the Tridimensional Personality Questionnaire (TPQ), and the serotonin-transporter genetic polymorphisms has been investigated with controversial results. The aim of the present study was to replicate this investigation and to establish the association for a Chinese population. Two polymorphisms of the serotonin transporter (5HTT-LPR, serotonin transporter-linked polymorphism region; 5HTT-VNTR, variable number tandem repeat polymorphism in intron 2 of the serotonin transporter gene) were determined for 192 healthy Han Chinese who had completed the TPQ. No significant differences were demonstrated for TPQ HA scores, including the sub-scales, for subjects with different 5HTT-LPR genotypes. A significantly higher HA2 sub-score was demonstrated for subjects carrying the 10-12 5HTT-VNTR genotype, however, compared with those from the 12-12 genotype group, for the male population (P = 0.007). Our findings suggest that the 5HTT genetic polymorphism may be associated with HA scores; however, the effect is influenced by ethnicity and gender.

Asian People↗
PubMed2001

Effects of occupation, lifestyle and genetic polymorphisms of CYP1A1, CYP2E1, GSTM1 and GSTT1 on urinary 1-hydroxypyrene and 2-naphthol concentrations.

This study was undertaken to determine the effects of occupation, lifestyle and the genetic polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2E1 (CYP2E1) and glutathione S-transferases micro1 (GSTM1) and 1 (GSTT1) on the concentrations of urinary 1-hydroxypyrene (1-OHP) and 2-naphthol among Korean coke oven workers and university students. The study subjects included 90 coke oven workers and 128 university students. A questionnaire was used to obtain detailed data about the work area, smoking habits and food intake of subjects. Associations between urinary polycyclic aromatic hydrocarbon (PAH) concentrations and occupation, smoking status, total airborne PAH level and genetic polymorphisms were tested. Urinary 1-OHP and 2-naphthol concentrations were higher in coke oven workers than in students and correlated significantly with work area. Urinary 2-naphthol concentrations increased with an increase in the level of cigarette smoking in students. Total airborne PAH level correlated with urinary 1-OHP concentration in coke oven workers. Urinary 1-OHP and 2-naphthol concentrations were higher in coke oven workers with the c1/c2 or c2/c2 genotype of CYP2E1 than in those with the c1/c1 genotype. Urinary 2-naphthol concentrations were higher in GSTM1-null workers than in GSTM1-positive workers. In multiple regression analysis CYP2E1 was a significant factor determining urinary 1-OHP concentrations in coke oven workers. CYP2E1 and GSTM1 were significant determinants for urinary 2-naphthol concentrations in coke oven workers and GSTM1 and smoking were prognosticators among university students. Urinary 1-OHP is a better indicator of occupational exposure to PAH in coke oven workers than 2-naphthol, whereas urinary 2-naphthol may be more sensitive for non-occupational inhalation exposure to PAH. In occupationally exposed populations CYP2E1 and GSTM1 appear to play an important role in the metabolism of pyrene and naphthalene. In individuals not occupationally exposed to PAHs GSTM1 and smoking seem to influence the urinary concentration of 2-naphthol.

Base Sequence↗
PubMed1993

Genetic polymorphism of inter-alpha-trypsin inhibitor (ITI) in the Basque Country (northern Spain).

The genetic polymorphism of inter-alpha-trypsin inhibitor (ITI) was analyzed in 2 samples of 554 residents and 303 autochthonous healthy unrelated individuals from the Basque Country (northern Spain), by isoelectric focusing on miniaturized polyacrylamide gels followed by immunoblotting. The allele frequencies were ITI*1 = 0.586, ITI*2 = 0.402 and ITI*3 = 0.012 in residents and ITI*1 = 0.548, ITI*2 = 0.449 and ITI*3 = 0.003 in the autochthonous population. These allele frequencies were compared with those reported in other European populations.

Alpha-Globulins↗
PubMed1999

Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics.

OBJECTIVE: To determine whether genetic polymorphisms of the beta2-adrenergic receptor gene affect the relationship between albuterol (INN, salbutamol) plasma concentrations and the forced expiratory volume in 1 second (FEV1) in subjects with moderate asthma. METHODS: Sixteen clinically stable patients with moderate asthma who participated in a pharmacokinetic-pharmacodynamic study of albuterol volunteered to provide a blood sample for determination of beta2-adrenergic receptor genotype. FEV1 and plasma concentrations of albuterol were determined at various times after administration of an oral solution that contained 8 mg albuterol. Patients withheld inhaled beta2-agonist and corticosteroid therapy 12 and 24 hours, respectively, before the study. beta2-Adrenergic receptor genotype was determined by polymerase chain reaction with allele-specific oligonucleotide hybridization. RESULTS: Albuterol-evoked FEV1 was higher and the response was more rapid in Arg16 homozygotes compared with the cohort of carriers of the Gly16 variant: Maximal percentage increase in FEV1 (%deltaFEV1), 18% versus 4.9% (P < .03); area under FEV1 albuterol concentration curve, 194%.mL/ng versus 30%.mL/ng (P < .05); initial slope (dE/dC), 1.43%.mL/ng versus 0.55%.mL/ng (P < .003). CONCLUSIONS: The beta2-adrenergic receptor gene polymorphism is a major determinant of bronchodilator response to albuterol. Future pharmacodynamic studies of beta2-agonists should include determination of 02-adrenergic receptor genotype.

Adrenergic beta-Agonists↗
PubMed2005

Genetic polymorphisms of oxidative and antioxidant enzymes and arsenic-related hypertension.

The association of 4 genetic polymorphisms, NAD(P)H oxidase, manganesesuperoxide dismutase (MnSOD), catalase, and endothelial nitric oxide synthase (e-NOS), was assessed with arsenic-related hypertension risk among 79 hypertensive cases and 213 controls in an arseniasis-hyperendemic area of Taiwan. Overall, MnSOD polymorphism significantly increased the risk of hypertension regardless of arsenic exposure. NADPH oxidase and eNOS polymorphisms were significantly associated with hypertension risk in the high arsenic exposure group; however, catalase polymorphism was not associated with hypertension. Groups were further stratified by triglyceride levels to evaluate whether the cumulative arsenic exposure combined the three polymorphisms together. The adjusted adds ratios (ORs) of at least two risk factors of the cumulative arsenic exposure and MnSOD, NADPH oxidase, and eNOS three-polymorphism combination versus any one risk factor of them were 0.8 (95% CI 0.3-2.3) for individuals with low triglyceride levels (<110 mg/dl) and 2.5 (95% CI 1.0-6.01) for high-triglyceride groups (>110 mg/dl), respectively. These results suggested that the NADPH oxidase, MnSOD, and e-NOS polymorphisms, but not catalase, might play a role in the development of arsenic-related hypertension, especially in subjects with high triglyceride levels.

Adult↗
PubMedDate not supplied

Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Iranian population.

1. The genetically polymorphic cytochrome P450 enzymes 2C9 (CYP2C9) and 2C19 (CYP2C19) are involved in the metabolism and elimination of a number of widely used drugs. The polymorphisms give rise to substantial interindividual and interethnic variability in drug excretion rates and final serum concentrations. For this reason, therapeutic responses and adverse drug reactions may vary from one person to another. In the present study we determined CYP2C9 and CYP2C19 genotypes in a random Iranian population to compare allele frequencies with previous findings in other ethnic groups. 2. Allelic variants of CYP2C9 (*1/*2/*3) and CYP2C19 (*1/*2/*3) were determined in 200 unrelated healthy Iranian volunteers by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. 3. Fifteen subjects (7.5%) were homozygous for the CYP2C9*2 allele, whereas 21 individuals (10.5%) were heterozygous for this allele and 164 subjects (82%) had the wild-type allele (CYP2C9*1). No CYP2C9*3 was detected in the population sampled. Six subjects (3%) were homozygous for CYP2C19*2, whereas 44 individuals (22%) were heterozygous for this allele. In the remaining subjects (75%), no CYP2C19*2 was found. In addition, no CYP2C19*3 was detected in the population sampled. 4. Based on our data, the frequency of the CYP2C9*2 allelic variant in Iranians is similar to that in other Caucasian populations; however, the frequency of the CYP2C9*3 allele differed significantly (P < 0.05). Conversely, there was no difference in the frequency of CYP2C19 allelic variants between the present study and other studies evaluating this allele in Caucasian populations (P > 0.05).

Adolescent↗
PubMed1991

A new genetic polymorphism in human platelet polypeptides detected by two-dimensional electrophoresis.

We described a new genetic polymorphism of human platelet polypeptide, detected by two-dimensional polyacrylamide gel electrophoresis followed by silver-staining. The polymorphism was tentatively designated thrombocyte B (ThB) with a molecular weight of 34 kDa and isoelectric point of 4.7-4.8. In this polypeptide, three different electrophoretic types (1-1, 1-2, 2-2) were identified. Family and population studies indicate that the three phenotypes of the polypeptide are determined by two common alleles at a single autosomal locus. In a Japanese population, the gene frequency of ThB 1/ThB 2 was 0.74/0.26. The ThB polypeptide was not found in other blood cells and decreased or disappeared during the preparation or storage of platelets.

Alleles↗
PubMedDate not supplied

A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals.

We have identified a genetic polymorphism of factor VII that is strongly associated with plasma factor VII coagulant activity (factor VIIc) in healthy individuals from the United Kingdom. This polymorphism was detected after Msp I digestion of polymerase chain reaction-amplified genomic DNA. In a sample of 284 men, the frequency of the M2 allele (loss of cutting site) is 0.1, and individuals with the M1M2 genotype have factor VIIc levels 22% below the sample mean (p less than 0.0001). Msp I genotype was found to be the strongest predictor of factor VIIc, accounting for 20.2% of the variance, with cholesterol accounting for an additional 3.5%. The base change that gives rise to the Msp I polymorphism is a G-to-A substitution in the codon for amino acid 353, leading to replacement of arginine (Arg) with glutamine (Gln) in the protein product of the M2 allele (designated Gln 353). Three individuals homozygous for the M2 allele have both low factor VIIc and low factor VII protein concentrations. The conformation of the Gln 353 molecule may be different from that of the Arg 353 protein, affecting its intracellular processing, secretion, turnover in plasma, or activity. In view of its association with lower factor VIIc levels, possession of the M2 allele may confer protection against thrombosis and myocardial infarction.

Aged↗
PubMed2004

CYP2C9 genetic polymorphisms and warfarin.

The objective of this study was to report 2 cases of CYP2C9 genetic polymorphism and elevated warfarin S:R ratios in patients taking low doses of warfarin, and compare the observed characteristics with those in published reports. Two patients of different age groups and races were evaluated for CYP2C9 genotype and warfarin S:R ratios. The patients had been stabilized on weekly warfarin doses of 10.5 mg and 10 mg, respectively. Each patient was found to have at least 1 variant CYP2C9 allele. Elevated warfarin S:R ratios in both patients provided evidence for impaired metabolism of S-warfarin. This report of a CYP2C9*3 heterozygous individual taking a low dose of warfarin is consistent with previous reports in the literature. This summary of a CYP2C9*6 homozygous individual taking a low dose of warfarin is the first such published report. CYP2C9 genotyping in these patients provided a likely explanation for their continued low warfarin dosage requirements. Awareness of a patient's CYP2C9 genotype may provide an explanation for low warfarin dosage requirements in stable patients and may help in determining the optimal dose in patients being initiated on warfarin.

Adult↗
PubMed1989

[Genetic polymorphism of AcP, EsD, 6-PGD and GPT in eleven ethnic groups of China].

The genetic polymorphism of red cell acid phosphatase (AcP), Esterase D (EsD), 6-phosphogluconate dehydrogenase (6-PGD) and Glutamic pyruvic transaminase (GPT) in eleven ethnic groups of China was studied by starch gel electrophoresis. The results of 2272 tested showed that the gene frequencies of AcPB1 in Dong, Hui, Bai, Tujia, Miao, Yi, Tibetan, Man, Yao, Hani, Buyi, etc. were 0.7835, 0.7958, 0.8137, 0.7750, 0.7624, 0.8038, 0.8075, 0.8035, 0.7725, 0.6488, 0.6896, EsD1 gene frequencies were 0.6418, 0.7315, 0.6005, 0.6025, 0.6411, 0.6411, 0.6558, 0.6305, 0.6020, 0.6023, 0.6368. 6-PGDA gene frequencies 0.9279, 0.9381, 0.9387, 0.9150, 0.9356, 0.9014, 0.7764, 0.8818, 0.9851, 0.9233, 0.9410. GPT1 gene frequencies 0.4075, 0.5367, 0.5049, 0.4824, 0.5322, 0.6106, 0.6313, 0.6400, 0.3985, 0.4930, 0.3976, respectively. In addition, some rare variants were found.

Acid Phosphatase↗
PubMed2004

Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas.

Cigarette smoke contains polycyclic hydrocarbons and arylamines that may both be activated by sulfotransferase, encoded by SULT1A1. A genetic polymorphism leads to an Arg213His substitution, thereby decreasing enzyme activity and stability and might thus modify the association between smoking and colorectal adenomas. We investigated this in a Dutch case-control study. Additionally, we evaluated potential roles of epoxide hydrolase (EPHX), N-acetyltransferases (NAT1 and NAT2) and glutathione S-transferases (GSTM1 and GSTT1). The data analysis included 431 adenoma cases and 432 polyp-free controls (54% women; mean age, 54.6 years) enrolled at endoscopy in 8 Dutch hospitals between 1997 and 2000. All participants provided data on smoking habits and blood for DNA isolation. Genotyping was performed using appropriate polymerase chain reaction-restriction fragment length polymorphism procedures. Multivariate models included age, sex, endoscopy indication, consumption of snacks and alcohol and, if appropriate, daily smoking dose or smoking duration. Smoking increased colorectal adenoma risk, most importantly by duration. Smoking for more than 25 years more than doubled adenoma risk (OR = 2.4, 95% CI = 1.4-4.1) compared to never smoking. Combinations of SULT1A1 fast sulfation (*1/*1) and of NAT2 slow acetylation with smoking resulted in a 4 times higher risk of adenomas compared to never smokers with other inherited gene variants, although there was no statistically significant effect modification. We found no clear effects of the other genetic polymorphisms on the association between smoking and adenomas. We conclude that smoking increases risk of colorectal adenomas and that SULT1A1 and NAT2 only modestly modify this association.

Acetyltransferases↗
PubMedDate not supplied

[Molecular and genetic polymorphism in three cattle breeds].

Determination of cattle breed and assignment of individual animals to that or another group based on distinctions of genotype is of great importance in genetics and selection. Using of PCR-analysis opened new possibilities for typing DNA. The procedure of PCR was optimized for animal DNA. Two methods of PCR, RAPD and SSRP, were applied for investigation of molecular-genetical polymorphism in three cattle breeds (Ukrainian red-motley lactescent, Golshtine and Simmental). A dendrogram reflecting genetical mutual relations between analyzed animals was drawn. The level of homo-heterozygosity and the distribution of microsatellite alleles were determined. System for investigation of molecular-genetical polymorphism in the cattle breeds and characterization of genotype of individual animals were developed and tested on a real population.

Animals↗
PubMed2003

[Relationship between tumor necrosis factor genetic polymorphisms and acute lymphocytic leukemia].

BACKGROUND & OBJECTIVE: Acute lymphocytic leukemia(ALL), which is sensitive to tumor necrosis factor (TNF) is one of hematological malignances derived from lymphoid tissue. Genetic polymorphisms in the tumor necrosis factor (TNF) locus can affect transcription and expression of TNF genes. This study was designed to investigate the relationship between -308 bp polymorphism in tumor necrosis factor-alpha(TNFalpha) gene and +252 bp in lymphotoxin-alpha(LTalpha) gene and the pathogenesis, clinical course, and outcome of ALL. METHODS: The single base mutation polymorphism in TNFalpha gene and LTalpha gene were analyzed among 29 Chinese patients with ALL and 72 normal controls using polymerase chain reaction (PCR)-restrictive fragment length polymorphism (RFLP). The clinical data were collected and survival analysis was performed. RESULTS: The difference of distribution of genotypes, alleles of TNFalpha(-308), LTalpha(+252), and TNF/LT polymorphic extended haplotypes between the ALL patients and control group were not statistically significant (P >0.05). In patients, no statistically significant association was found between the presence of a given TNF/LT haplotype status and clinical characters such as sex, white blood cell (WBC) counts, central nervous system involvement, and the response to therapy(P >0.05). The estimated 1-year overall survival rates in the groups of patients carrying high-risk and low-risk haplotypes were not statistically significant (P >0.05) using Kaplan-Meier method. In multivariate Cox regression models the TNF/LT haplotype status was not found to be a risk factor for outcome (P >0.05). CONCLUSION: These data suggest that genetic polymorphisms in the TNFalpha(-308) and LTalpha(+252) are not crucial in the pathogenesis, clinical course, and outcome of ALL patients.

Adolescent↗
PubMed2006

Genetic polymorphisms of phase II metabolic enzymes and lung cancer susceptibility in a population of Central South China.

A case-control study was conducted for analyzing the genetic polymorphisms of phase II metabolic enzymes in 97 patients with lung cancer and 197 healthy subjects from Han ethnic group of Hunan Province located in Central South China. The results showed that the frequencies of glutathione S-transferase (GST) M1-null (GSTM1-) or GSTT1-null (GSTT1-) genotype alone, or combined form of both in lung cancer patients were significantly higher than those of the controls. Genotypes of combining GSTP1 mutant/GSTM1(-) or GSTP1 mutant/GSTT1(-) led to high risk of lung cancer. Individuals carrying any two or all three of GSTM1(-), GSTT1(-) and GSTP1 mutant genotypes have a distinctly increased risk of lung cancer when compared to those with GSTM1 present (GSTM1+: GSTM1+/+ or GSTM1+/-), GSTT1 present (GSTT1+: GSTT1+/+ or GSTT1+/-) and GSTP1 wild genotypes. Furthermore, individuals possessing combined genotypes of N-acetyltransferase 2 (NAT2) rapid acetylator, GSTP1 mutant and both GSTT1(-) and GSTM1(-) have a remarkably higher lung cancer risk than those carrying combined NAT2 slow acetylator genotype, GSTP1 wild genotype and both GSTT1(+) and GSTM1(+) genotypes. All these findings suggest that the genetic polymorphisms of phase II metabolic enzymes affect the susceptibility of lung cancer in the Han ethnic group of Central South China.

Adult↗
PubMed2006

Genetic polymorphism of metabolic enzymes modifies the risk of chronic solvent-induced encephalopathy.

In the present study, we investigate whether genetic polymorphism in enzymes involved in the metabolism of organic solvents influences susceptibility to chronic solvent encephalopathy (CSE), which is one of the major effects of long-term exposure to organic solvents. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1 enzymes were determined in a group of male CSE patients (N=97) and controls (N=214). The selection of the patients was based on a standard diagnostic protocol, including interviews, neuropsychological tests and questionnaires directed to somatic, cognitive and mood symptoms and exposure, in combination with well-defined decision rules. As controls, healthy workers of similar socio-economic background, without memory problems and with no known exposure to organic solvents, were included in the study. Comparing patients and controls, higher frequencies of the variant *5B allele of the CYP2E1 gene (OR: 5.8; 95% CI: 1.8-18.8) and of the variant GSTP1*C allele (OR: 0.40; 95% CI: 0.17-0.94) were found. Homozygous carriers of the exon 4 EPHX1 Arg139 variant allele had a lower risk (OR: 0.25; 95% CI: 0.06-1.13). The present study indicates that genetic polymorphism of CYP2E1, EPHX1 and GSTP1 modify the risk of developing CSE.

Adult↗
PubMed2006

Genetic polymorphisms of the CYP19A1 gene and breast cancer survival.

The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus may be related to the progression of breast cancer. We examined the association between CYP19A1 genetic polymorphisms and breast cancer survival in a cohort of 1,136 patients who were recruited as part of a population-based case-control study in Shanghai, China from 1996 to 1998 and who has donated a DNA sample to the study. Patients were followed for cancer recurrence and mortality through July 2005. Nineteen haplotype tagging single-nucleotide polymorphisms (SNP) in the CYP19A1 gene were evaluated. For each of the five SNPs located in haplotype block 2, patients homozygous for the minor alleles had a reduced 5-year disease-free survival rate compared with those carrying the major allele. The age-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were 1.5 (1.1-2.1), 2.1 (1.2-3.6), 1.5 (1.1-2.0), 1.4 (1.0-2.0), and 1.4 (1.0-2.0) for hCV1664178, rs12900137, rs730154, rs936306, and rs1902586, respectively. Haplotype analyses showed that the haplotype CCCTA (all minor alleles of the five SNPs in block 2) was associated with decreased disease-free survival (HR, 1.9; 95% CI, 1.1-3.3). The nonsynonymous SNP, rs700519 (Arg264Cys), located in haplotype block 4, was also associated with breast cancer survival. The age-adjusted HR for the Cys/Cys (T/T) genotype was 2.2 (95% CI, 1.2-4.1) for overall survival and 2.1 (95% CI, 1.1-3.9) for disease-free survival, compared with those carrying the Arg (C) allele. These results suggest that polymorphisms in the CYP19A1 gene may have effects on breast cancer prognosis.

Adult↗
PubMed2000

HBV/HCV Infection, Alcohol, Tobacco and Genetic Polymorphisms for Hepatocellular Carcinoma in Nagoya, Japan.

A population-based case-control study was carried out to investigate risk factors for hepatocellular carcinoma (HCC) in Nagoya, Japan, including hepatitis virus infections, drinking and smoking habits and genetic polymorphisms in aldehyde dehydrogenase2 (ALDH2) and cytochrome P4502E1 (CYP2E1). A total of 84 patients with HCC and 84 sex, age and residence pair-matched controls were recruited for this study. By univariate analysis, hepatitis B virus (HBV) (OR=5.14; 95%CI=2.29-11.6) and hepatitis C virus (HCV)(OR=32.00; 95%CI=7.83-130.7) infections, having a history of blood transfusion (OR=5.25; 95%CI=1.80-15.29), and habitual smoking (OR=2.36; 95%CI=1.17-4.78) were significantly linked to cases; by multivariate analysis, HCV infection (OR=23.5; 95%CI=5.07-108.9) and habitual smoking (OR=5.41; 95%CI=1.10-26.70) were still associated with a significantly increased risk. The c1/c1 genotype of CYP2E1 (odds ratio [OR]= 0.45; 95% confidence interval [CI]=0.21-0.99), detected by Pstl and Rsal digestion was significantly more prevalent in the control group, while 1-1 genotype of ALDH2 (OR=1.24; 95%CI=0.70-2.20) did not demonstrate variation. There were no statistically significant interactions between habitual smoking/drinking and genetic polymorphisms of ALDH2/P4502E1 with reference to HCC development. These findings suggest that viruses, especially HCV infection, and habitual smoking are major independent risk factors, while genetic polymorphisms of ALDH2 and CYP2E1 have only limited contribution to the risk of HCC in Nagoya, Japan.

Journal Article↗