Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genetic polymorphisms”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources
PubMed1997

Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and human esophageal squamous cell carcinoma susceptibility.

Many human cancers are caused by synthetic or natural chemical compounds in the environment. Esophageal squamous cell carcinoma has been reported to be epidemiologically associated with tobacco and alcohol consumption. We studied the association between genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and esophageal squamous cell carcinoma susceptibility. We examined genetic polymorphisms of the CYPIA1, GSTM1, CYPIIE1, ADH2, and ALDH2 genes in 94 Japanese patients with esophageal squamous cell carcinoma and 70 unrelated healthy Japanese persons. There were no significant differences between healthy controls and patients with esophageal cancer in the polymorphisms of the CYPIA1, GSTM1, and CYPIIE1 genes. On the other hand, there were significant differences in the ADH2 and ALDH2 polymorphisms between healthy controls and esophageal cancer patients. The ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) genotypes were independently and significantly higher in esophageal cancer patients than in healthy controls. Furthermore, persons with the combined genotypes ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) were at extraordinarily high risk for esophageal squamous cell carcinoma, with an odds ratio of 17.9 (p < 0.001). Thus polymorphisms of alcohol-metabolizing enzymes, that is, ADH2 and ALDH2, may be useful for screening patients at high risk for esophageal cancer, which might facilitate clarification of esophageal tumorigenesis and prevention of esophageal cancer.

Alcohol Dehydrogenase↗
PubMed2006

Genetic polymorphism of CYP2E1 and digestive tract alcohol damage among Polish individuals.

BACKGROUND: Genetic polymorphism of enzymes involved in alcohol metabolism plays a relevant role in etiopathogenesis of alcohol disease. The aim of the present study was to find in the Polish population the CYP2E1 genotypes that are likely to be responsible for higher susceptibility to alcohol disease of the liver and chronic alcohol pancreatitis. METHODS: The CYP2E1 genotype and c1 and c2 alleles frequency were examined in 198 patients. Genotyping of the CYP2E1 was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. RESULTS: In the examined population encompassing 198 subjects, the c2 allele was present only in 1.5% of patients. It was found only in patients abusing alcohol. In the group of patients with alcoholic cirrhosis, it was present in 3.5% of cases, whereas in patients with chronic alcoholic pancreatitis, in 2.3%. The genotype c1/c2 was present in 3% of subjects. The genotype c2/c2 was not found in any patient. Heterozygotes c1/c2 were present only in patients consuming excessive amounts of ethanol; in 7% of patients with alcoholic cirrhosis and in 4.5% of those with chronic alcoholic pancreatitis. The c2 allele occurred only in men. None of the examined women had the genotype c1/c2. CONCLUSIONS: Our studies suggest that the frequency of the c2 alleles in Polish population is low. Because of their rare frequency, it is difficult to conclude explicitly that the presence of the c2 allele promotes alcoholic damage to alimentary organs among Poles. It seems, however, that they pose the risk of alcoholic cirrhosis; their role in chronic alcoholic pancreatitis is difficult to assess.

Adult↗
PubMed1986

Genetic polymorphism of the seventh component of complement: a new variant.

Genetic polymorphism of the seventh component of complement (C7) was studied by the methods of agarose gel isoelectric focusing and immunoblotting. Serum or plasma samples were treated with neuraminidase prior to isoelectric focusing. A cathodal variant, named C7 5, was recognized in the treated samples. Family study indicates that the C7 5 component is genetically determined. The allele frequencies calculated from 183 healthy Japanese individuals were C7*1 = 0.809, C7*2 = 0.104, C7*4 = 0.038, and C7*5 = 0.049. An association between C7 and C6 alleles was not found.

Alleles↗
PubMed1998

Association of genetic polymorphisms in the ACE, ApoE, and TGF beta genes with early onset ischemic heart disease.

BACKGROUND: The genetic factors that contribute to ischemic heart disease (IHD) are poorly understood, and it is likely that multiple genes acting independently or synergistically contribute to the risk of IHD and outcome. The genes for angiotensin-converting enzyme (ACE) and apolipoprotein E (ApoE) have been implicated independently in the risk of IHD. HYPOTHESIS: This study examined whether genetic polymorphisms in the ACE and ApoE genes are associated with early onset IHD. Polymorphisms in a third gene, transforming growth factor beta 2 (TGF beta 2), with a known role in wound repair and cardiac development, are also examined with respect to early onset IHD. METHODS: In all, 101 patients with IHD and onset of disease before 55 years for men and 60 years for women, and 100 controls with angiographically confirmed normal coronary arteries were recruited for this study. The ACE, ApoE, and TGF beta 2 genotypes were determined by polymerase chain reaction amplification or Southern blotting and were compared with the patient's clinical and family histories. RESULTS AND CONCLUSION: The frequency of the ACE D allele was significantly lower in the patient group (0.475) than in the control group (0.59, p = 0.03), which was attributed to a reduction in the number of patients with the DD genotype (patients: 24% DD, controls: 33% DD). Sudden cardiac death was also associated with the DD genotype. These data are consistent with the ACE D allele contributing to a fatal outcome. No association between the DD genotype and risk of myocardial infarction, presenting age, extent of vessel disease, family history, hypertension, or hypercholesterolemia was seen. Analysis of the ApoE genotype showed no association with early onset IHD. There was no evidence for a synergistic effect between the ACE and ApoE genotypes on the risk of early onset IHD. A polymorphism in the TGF beta 2 gene was rare and not associated with early onset IHD.

Adult↗
PubMed1999

Apolipoprotein E and methylenetetrahydrofolate reductase genetic polymorphisms in relation to other risk factors for cardiovascular disease in UK Caucasians and Black South Africans.

Genetic polymorphisms for apolipoprotein E (apo E) and methylenetetrahydrofolate reductase (MTHFR) are believed to modulate risk of coronary heart disease (CHD) acting through regulation of lipid and homocysteine metabolism, respectively. The distributions of apo E and MTHFR alleles in Black South Africans, a population with a low CHD incidence, and UK Caucasians from the Cambridge area, with a higher CHD incidence, were therefore compared. Clinically healthy volunteers (207), including 107 UK Caucasians from the Cambridge area and 100 Black South Africans, participated in the study. Apo E and MTHFR genotypes were determined in all of them. Analyses for serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and plasma fibrinogen were carried out in 65 UK Caucasians and 60 Black South Africans. The apo E epsilon4 allele, which is associated with elevated CHD risk, was present in 48% of Black South Africans compared to 20.8% of Caucasians (P < 0.0001); however, both total and LDL cholesterol levels in Black South Africans were 18-32% lower than in Caucasians with similar apo E genotypes. Hyperhomocysteinemia-causing MTHFR 677T variant was detected in only 20% of Black South Africans (no homozygotes) versus 56% of Caucasians with 12% homozygotes (P<0.0001). Our findings suggest that the potentially unfavourable pattern of apo E allele distribution in Black South Africans does not result in increased CHD incidence due to protection by dietary and/or other life style related factors. The exceptionally low frequency of MTHFR mutant homozygotes in this population suggests that this polymorphism should not be regarded as an important CHD risk factor among Black South Africans.

Alleles↗
PubMed1999

N-acetyltransferase 1 genetic polymorphism influences the risk of prostate cancer development.

The potential involvement of N-acetyltransferase 1 (NAT1) genetic polymorphisms in prostate cancer (PCa) patients was analyzed in 101 patients with PCa and 97 controls with no incidental malignancy. Identification of NAT1*10, the variant allele associated with the rapid acetylator phenotype was by allele-specific polymerase chain reaction (PCR). When the NAT1*10 heterozygote and other genotypes without NAT1*10 allele were considered as low risk genotypes, NAT1*10/NAT1*10 had a significantly higher risk of PCa (OR = 2.4, 95% CI; 1.0-5.6). If our preliminary results can be confirmed in a larger population, it may be a useful marker for PCa risk.

Alleles↗
PubMed1996

Frequencies of five genetic polymorphisms in coronarographed patients and effects on lipid levels in a supposedly healthy population.

Allele frequencies of genetic polymorphisms were compared between supposedly healthy subjects and angiographically proven coronary artery disease patients. The polymorphic candidate loci investigated were the apolipoprotein (apo) B signal peptide and XbaI polymorphism, the apo E polymorphism and two polymorphism of lipoprotein lipase (LPL) gene: Hind/III and PvuII. Apo B signal peptide and HindIII/LPL polymorphisms showed significant differences in allele partition between cases and controls; the rare alleles of both polymorphisms were less frequent (p < 0.05) in cases. We looked for associations between the polymorphisms and lipid concentration variability in a supposedly healthy population (145 men and 144 women). Apo B signal peptide, apo E and PvuII/LPL polymorphisms seem to influence some lipid metabolism parameters significantly. Apo AI and LpCIII levels were significantly different among apo B signal peptide genotypes: Del homozygotes had the highest concentrations of both variables. The epsilon 4 allele of apo E polymorphism was associated with increased concentrations of total cholesterol, LDL cholesterol and apo B. Increased LpAI:AII levels observed in E3 homozygotes (p < 0.01) have not previously been reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.

Adult↗
PubMed2001

[Molecular genetic polymorphism of the genes of neurotransmitter systems in schizophrenics with early manifestation of the disease].

Molecular-genetic polymorphism of genes-candidates was investigated: the genes of serotonin receptor--type 2a (HTR2A), dopamine receptor gene--type 2, serotonin transporter (5HTTLPR). Thirty one schizophrenic patients whose age was 12.6 +/- 3.6 years at the onset of the disease and 208 patients whose age was 23.5 +/- 6.7 years at the onset of the disease were examined. The frequencies of HTTLPR and DRD2 genotypes differed insignificantly in both groups. The distribution of 5HTR2A genotypes in the schizophrenic group with an early manifestation of the disease differed from that with a later manifestation significantly (chi 2 = 6.27; df = 2; p = 0.044). The relative risk (odds ratios) was 7.9 with 95% significance interval 1.008-61.94; p = 0.045. The severity of the disease and a positive family history were also examined in A2A2 genotype carriers. A positive family history was found in 9 (52.9%) of the 17 schizophrenics with an early manifestation and only in 15 (21.1%) of 71 patients of the similar group with a later one. Assessment of the clinical symptoms revealed that the total scores by the negative symptomatology subscale (PANSS) was higher in the patients with an early manifestation than in those with later one; but these differences did not achieve the significance level. These and earlier findings lead to the conclusion that A2A2 genotype was more frequently observed in the patients with more pronounced negative symptoms and high hereditary burden, which suggests that the A2A2 genotype is associated with an early onset.

Adult↗
PubMed1990

Genetic polymorphism of Na-K cotransport in essential hypertension.

Erythrocyte Na-K cotransport is high and genetically correlated to hypertension in Milan hypertensive strain (MHS) rats. In man there is a substantial overlap of individual values between essential hypertensives and controls. However, the findings in rat strains with different types of genetic hypertension suggest that Na-K cotransport studies may throw light on the different pathogenetic mechanisms of the human disease. In 28 normotensive and 22 hypertensive families the midparent-offspring correlation of Na-K cotransport values was significant only in hypertensive families (r = 0.48) and not significant in normotensive ones (r = 0.06), indicating genetic polymorphism for its phenotypic expression only in the hypertensives. In 189 essential hypertensives and 109 normotensives carefully selected from a population-based screening in order to exclude uneven sampling bias, analysis for the bimodality of the distribution of Na-K cotransport clearly showed that normotensives are distributed unimodally and hypertensives bimodally, with nadir of the distributions at about 450 mumols (1 RBC/h). Dividing the hypertensives according to Na-K cotransport value, the high Na-K cotransport subgroup has lower fractional percent excretion of uric acid and plasma renin activity. These data suggest that the high Na-K cotransport subgroup has peculiar characteristics of greater proximal tubular reabsorption (lower fractional excretion of uric acid) that may cause body volume expansion (lower plasma renin activity).

Biological Transport, Active↗
PubMedDate not supplied

Genetic polymorphisms of hormone-related genes and prostate cancer risk in the Japanese population.

Carcinogenesis of the prostate involves androgen influences, and associations between genetic polymorphisms of androgen receptor and metabolizing enzymes and prostate cancer risk have been reported. Roles for non-androgenic hormones are not well defined, but they also may have an impact judging from epidemiological and animal experimental alphalambda zeta of data. The purpose of the study was to determine whether hormone-related polymorphisms are associated with prostate cancer risk. A case-control study was performed with 147 Japanese prostate cancer patients and 266 urological controls. Polymorphisms of target genes [cytochrome P450 (CYP) 1B1, Leu432Val; debrisoquine hydroxylase, (CYP2D6)*4; aromatase (CYP19), Arg264Cys; estrogen receptor (ER)alpha-Xx (Xba I) and Pp (Pvu II); ERbeta-Rr (Rsa I); progesterone receptor (PR) Alu in intron 7] were examined by PCR-based methods. The capital and small letters signify the absence and presence of restriction sites, respectively. Odds ratios (OR) were adjusted for age using multiple logistic regression analysis with SPSS Medical Pack. Among the seven examined genetic polymorphisms, significant associations between CYP1B1 Leu432Val (OR 4.80; 95% confidence interval (CI), 1.21-19.05) and Alu in intron 7 of PR (OR 4.17; 95%CI, 1.26-13.85) were found. As for combined effects, the CYP1B1 polymorphisms (Leu/Val+Val/Val) together with heterozygosity for Alu in the PR were more frequent among prostate cancer patients (1.45%) than controls (0.41%), although without significance (OR, 3.99; 95%CI, 0.36-44.8). The combination of ERalpha (P/p+p/p) polymorphisms with heterozygosity for Alu in the PR demonstrated an OR of 4.56 (95%CI, 1.01-20.6). This pilot study showed that CYP1B1 and PR polymorphisms, alone or in combination, might be associated with prostate cancer risk. They might, therefore, have potential as a tool for identifying high-risk individuals.

Adenocarcinoma↗
PubMed1986

[Stability and/or variability of the expression of genetic polymorphism of hydroxylation and acetylation in patients with various pathologies and under various treatments].

During the last decade, the Drug Monitoring allowed the clinician to control the efficiency and/or the toxicity of the used drugs. This control is of a posteriori type. The discovery of the various genetic polymorphisms (acetylation, oxidation), the use of probe drugs (caffeine, sulfadimidine, dapsone, debrisoquine, sparteine) and the fact that other drugs exhibit the same polymorphisms as the probe drugs gave the opportunity to develop non invasive methods, to study in population the distribution of the various genetic tracts, to check the subjects who might be at risk toward a drug. Can, the obtained results in simple situation be extrapolated to complex pathological or therapeutic situations? Among patients with side and/or toxic effects of the drugs, there is a significant increase of the poor metaboliser (PM) status of debrisoquine. But it is necessary to carefully check the state of the patients before phenotyping them (drug, hepatic, metabolic, renal diseases). If the patients are taking drugs which share the same genetic polymorphism as debrisoquine during the time where the phenotype is established, some misfits can happen. The patients taking propafenone present a false PM status of debrisoquine. This is less obvious with mexiletine. In a population of 200 epileptics neither the disease nor the therapeutics seem to modify the distribution of the two phenotypes PM and EM. All things considered we do not know exactly the limits of use of these tests in the patients. We need more data to validate the advices dealing with the use of pharmacogenetic concepts as a provisional tool for patient cares?

Acetylation↗
PubMed2005

Association of endometriosis risk and genetic polymorphisms involving sex steroid biosynthesis and their receptors: a meta-analysis.

Endometriosis is a sex steroids-dependent disease. It has been postulated that certain genetic polymorphisms involved in sex steroids biosynthesis and metabolisms may be associated with increased risk of developing endometriosis. Despite a deluge of reports of positive associations of endometriosis with numerous polymorphisms involving sex steroids production and metabolism, the results are often conflicting. We performed a meta-analysis of 12 association studies on 5 genes (CYP17, CYP19, AR, PR and ER). We found that many reported positive findings were not supported by the data due to faulty analysis. There have been no functional data that support a putative relationship of these genetic polymorphisms with endometriosis. A handful of positive findings so far have not been independently replicated, and should be viewed as preliminary. In addition, these findings should be counterbalanced by legitimate concerns of multiple comparisons, small prior probability of association with a particular polymorphism, proper selection of controls, and lack of replication (at least until now). In future association studies, it may be productive to put more thought to study design, execution, and data analysis.

Aromatase↗
PubMed2006

Genetic polymorphism of vascular endothelial growth factor: impact on progression of IgA nephropathy.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in the capillary endothelial cell growth and proliferation and has known effects on glomerular microvascular permeability. Because certain VEGF polymorphisms are correlated with alterations in VEGF expression, we hypothesized that VEGF genetic polymorphisms may affect the renal survival and progression of primary IgA nephropathy. METHODS: The study population consisted of 195 biopsy-proven IgA nephropathy patients at our center between 1984 and 2004. VEGF genotype polymorphism at -2578 positions was determined from peripheral blood leukocytes DNA using polymerase chain reaction methodologies. The primary end point was kidney survival as measured by the time interval from renal biopsy to end-stage renal disease or the requirement of renal replacement therapy. RESULTS: In total, we studied 119 women (61%) and 76 men (39%), with a mean age of 35 +/- 10 yr at the time of renal biopsy. Observed genotype frequency was 55.6%, 38.8%, and 5.1% for CC, CA, and AA genotypes respectively. Baseline characteristics did not differ significantly between three genotype groups for patient age, sex, prevalence of hypertension, degree of proteinuria, initial serum creatinine concentration, and the histological grading. After a median follow-up period of 11 yr, doubling of the baseline serum creatinine occurred in 107 of them; 99 patients reached end-stage renal disease requiring renal replacement therapy with a median renal survival of 88 months. The kidney survival in the CC genotype subgroup was similar to that of the CA/AA genotype subgroup during the first 2 yr but became worse than the latter thereafter (log-rank test P = 0.023). The kidney survival rates at the end of 6 yr were 76.8% in the CA genotype, 67.0% in the CC, and 50.0% in the AA genotype groups. Unadjusted hazard ratio of developing end-stage renal disease was 2.65 (95% CI, 1.16 to 6.06) for the CC group as compared to the CA/AA group. The influence of VEGF genotype upon renal survival, however, was not significant after multivariate Cox regression analysis. CONCLUSION: Our preliminary results raise the concern that the CC genotype of the VEGF promoter at -2578 position might be associated with increased risk of renal progression in patients with IgA nephropathy.

Adolescent↗
PubMed2003

[DNA mismatch repair enzyme hMSH2 genetic polymorphism in southern Chinese Han population].

OBJECTIVE: To study hMSH2 genetic polymorphism in southern Chinese Han population. METHODS: The basic materials and blood samples from 163 southern Chinese were collected. The mutations of exon 6 and exon 7 of hMSH2 gene were investigated by PCR-SSCP, followed by DNA sequencing. RESULTS: Fragments of 250 bp including exon 6 and fragments of 323 bp including exon 7 of hMSH2 gene were amplified by multiple PCR. The allele frequencies of C18, A82 and B39 type mutations were 0.0184, 0.0031, 0.0031, respectively. The gene frequencies and gene type frequencies of three polymorphism sites in normal population accorded with Hardy-Weinberg equilibrium (P>0.05). The heterozygosity of C18 type mutation (0.0361) was the highest. CONCLUSION: There were three polymorphism sites in exon 7 of hMSH2 gene in southern Chinese Han population, among which the genotype frequency of C18 type was the highest, suggesting that C18 type mutation be a useful genetic mark.

Asian People↗
PubMed1993

Dog genetic polymorphism revealed by synthetic tandem repeats.

We are studying the genetic polymorphism associated with Variable Number of Tandem Repeat (VNTR) loci in 13 breeds of dogs, namely: Alaskan Malamute, Barzoi, Beagle, Belgian Shepherd, Fox Terrier, Griffon, Labrador, Irish Setter, Spaniel, Dachshund, Irish Terrier, Shar Pei and Poodle. Our approach is based upon synthetic tandem repeats (STRs). Using a panel of these arbitrary unit polymers to detect minisatellites, we are attempting to develop paternity testing systems on pure bred dog pedigrees. We are evaluating the potential importance of STRs as a tool for the isolation of minisatellites in dogs, as well as for the characterization of dog genetic markers.

Animals↗
PubMed2003

Genetic polymorphisms in biotransformation enzymes in Crohn's disease: association with microsomal epoxide hydrolase.

BACKGROUND: Mucosal biotransformation enzymes can modify toxic compounds in the gut. As chemical or oxidative stress may be involved in the aetiology of Crohn's disease, genes encoding for enzymes involved in the prevention of such stress may be candidates for genetic susceptibility to Crohn's disease. AIM: To assess the association of Crohn's disease with genetic polymorphisms in cytochrome P450 1A1, glutathione S-transferases mu-1, pi-1, and theta-1, and epoxide hydrolase. METHODS: chi(2) square analysis was used to compare frequencies of polymorphisms between 151 patients with Crohn's disease and 149 healthy controls. RESULTS: In patients, a genetic polymorphism in exon 3 of the microsomal epoxide hydrolase gene was distributed significantly different compared with controls (chi(2)=23.7; p<0.0001). All other polymorphisms tested were equally distributed between patients and controls. CONCLUSIONS: Microsomal epoxide hydrolase may play a role in the pathophysiology of Crohn's disease. Furthermore, the epoxide hydrolase gene is located on chromosome 1q, close to a region previously linked to Crohn's disease.

Adult↗
PubMed2003

Influence of polymorphism (RFLP-sstI) at the apolipoprotein C-III gene locus on the lipoprotein metabolism and insulin resistance in essential hypertensive patients. Interaction between gender and genetic polymorphism.

BACKGROUND AND AIM: With respect to the general population, hypertensive patients show an increase in plasma total cholesterol and triglycerides, a decrease in HDL-cholesterol (HDLc) and a higher degree of insulin resistance. Apolipoprotein C-III (apo C-III) plays a regulatory role in the catabolism of triacylglycerol-rich lipoproteins. The S2 allele has been associated with elevated plasma triglycerides concentration, blood pressure and increased risk of myocardial infarction, all of which are characteristic of an insulin resistant state. The aim of this study was to investigate the SstI polymorphism of the apo C-III gene locus on the lipoprotein metabolism, apolipoproteins and basal glucose and insulin levels in essential hypertensive patients. We also examined the influence of the S1S2 allele on blood pressure and the interaction of the mutation at the apo C-III gene and the gender. METHODS AND RESULTS: We studied 104 essential hypertensive patients (59 males and 45 females) determining the carriers of the S2 allele of the genetic polymorphism in the apo C-III gene by polymerase chain reaction, lipoprotein metabolism by standard laboratory methods and ultracentrifugation, apolipoproteins A-I and B by immunoturbidimetry and basal glucose and insulin levels by enzymatic method and radioimmunoassay, respectively. The frequency for the carriers of the SstI minor allele S2 (S1S2 genotype) was 0.17. Patients with the rare S2 allele compared with those with S1S1 allele showed higher plasma triglycerides, total cholesterol and apo B (255.9 +/- 114.6 vs 135.8 +/- 89.1; 250.6 +/- 56.6 vs 214.8 +/- 47.9 and 128.7 +/- 34.8 vs 103.1 +/- 28.6 respectively). Furthermore, basal glucose, insulin levels in S2 allele, and the rate Tg-VLDL/HDLc were increased in the same group. Subgroup analysis revealed that the association between these polymorphism and lipoprotein metabolism, apolipoprotein and basal glucose and insulin levels occurred predominantly in females. A study on the effect of the interaction between this mutation with gender revealed an additive effect on changes in total triglycerides levels. However age, blood pressure and body mass index were similar in both groups of patients (S1S1 and S1S2 genotypes). CONCLUSIONS: These results provide evidence of interaction between gender and the Sst1 polymorphism of the apo C-III on lipoprotein metabolism and insulin resistance in essential hypertensive patients. However, the studied mutation does not contribute to blood pressure levels in essential hypertensive patients (crossover study).

Adult↗