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 1,747 records · Page 97Linked to original sources

The role of candidate genetic polymorphisms in the etiology of prostate cancer.

Prostate cancer appears to result from complex interactions among genetic, endocrine and environmental factors. Identification of risk factors for development and progression of prostate cancer is needed. This will allow researchers to design strategies to reduce the morbidity and mortality from this cancer and to identify individuals at increased risk of developing the disease. It is probable that common genetic polymorphisms (variants) in genes directly and indirectly involved in androgen biosynthesis, metabolism and regulation are important. Other important genes are likely to be those directly involved in regulation of prostate cell proliferation and apoptosis.Prostate Cancer and Prostatic Diseases (2000) 3, 236-240

Journal Article↗

Genetic polymorphism of N-acetyltransferase and glutathione S-transferase related to neoplasm of genitourinary system. Minireview.

Genetically determined risk factors may considerably contribute to the development of neoplastic diseases, including neoplasm of urinary organs, e.g. bladder and prostate cancers. It is believed that they may result, among others, from the differences in the metabolism of environmental carcinogens and mechanisms of DNA repair. There is a clear evidence that the kind and rate of metabolism is genetically determined by polymorphic enzyme coding genes participating in the process of xenobiotic transformation. Genetic polymorphism has been confirmed for a number of enzymes involved in the reaction of oxidation or conjugation of exo- and endogenous xenobioties. Gene variability may alter the expression or enzymatic activity of coded enzymes. Therefore, the cancer risk assessment should also be based on individual differences in the ability to activate (phase I) or to detoxify (phase II) possible carcinogens. In the present study, the information on the significance of glutathione 5-transferase (GST) and N-acetyltransferase (NAT) gene families in protection of human health and incidence of various diseases is summarized. The role of hereditary polymorphisms of GST and NAT genes involved in the etiology of neoplasm of urinary organs is controversial. That is why, special attention has to be focused on the recent information on a possible role of GST and NAT polymorphisms in the predisposition to urinary bladder, prostate and urothelial transitional cell carcinoma.

Arylamine N-Acetyltransferase↗

No potential role of genetic polymorphisms for IL-4, IL-13 and IL-4 receptor in respiratory allergy: a study in adults working at social welfare facilities in Korea.

Indoor air in public facilities contains various pollutants jeopardizing the health of employees or occupants in the facilities. We evaluated the respiratory allergy-related immune status of employees, and investigated a role of genetic predisposition on respiratory allergy occurrence in the employees. Among 23 workers from 5 facilities, 48% were positive for aeroallergens. House dust mite was the major allergen demonstrating positive skin reactions. The level of plasma IgE, an immunologic marker for allergic hypersensitivity induction, was upregulated in the allergy positive employees. The percentage of eosinophils in peripheral blood was also higher in the allergy positive employees than in the employees with negative skin test results. We also evaluated genetic polymorphisms on interleukin-4 (IL-4) receptor alpha chain (Gln576Arg and Ile50Val), IL-4 (C589T) and interleukin-13 (Arg130Gln), which has been implicated in asthma induction in children. However, no higher frequencies of these genetic variations were found in the adults with positive skin test results for aeroallergens. This study implies that workers in social welfare facilities may have a substantial risk of suffering from respiratory allergy associated with exposure to aeroallergens, but genetic variations in the IL-4 receptor alpha chain, IL-4 and IL-13 may not be critical in adult workers for the development of respiratory allergic diseases.

Adult↗

Genetic polymorphism in human apolipoprotein E.

This chapter provides the methodologies employed to study the polymorphism of human apoE. These and other related studies have advanced our understanding of the structure and function of this protein as follows: The complex array of human apoE observed by two-dimensional gel electrophoresis results from genetic variation and posttranslational modification. The genetic polymorphism of apoE is explained by the existence of three common alleles (epsilon 4, epsilon 3, epsilon 2) at a single structural gene locus. Combinations of above alleles can generate three homozygous (E4/4, E3/3, E2/2) and three heterozygous (E4/3, E3/2, E4/2) apoE phenotypes. The apoE phenotype E2/2 is found in 91% of patients with type III hyperlipoproteinemia and can be used as a molecular marker for the diagnosis of this disease. However, other rare or common apoE phenotypes have been observed in patients with type III HLP. ApoE originating from E2/2 phenotype (Arg 158 to Cys 158 substitution) has reduced affinity for the LDL receptor. This property of apoE2 can account partially for the accumulation of apoE-rich lipoprotein remnants in the plasma of patients with type III HLP. However, other genetic or environmental factors are necessary for the phenotypic expression of the disease.

Apolipoproteins E↗

[Genetic polymorphism of vitamin D receptor and osteoporosis].

BACKGROUND: Genetic factors condition an important part of bone mass. The role of vitamin D receptor polymorphism (VDR) as genetic marker of osteoporosis is a matter of discussion. We have studied the possible influence of VDR on bone remodelling, calciotropic hormones, on the presence of osteoporosis and osteoporotic bone fractures. PATIENTS, CONTROL POPULATION AND METHODS: A case-control study. We have studied a total of 127 postmenopausal Canarian women from Canary Islands, Spain; 66 healthy controls and 61 with the diagnosis of osteoporosis, which was made by clinical, radiological and densitometric criteria. 17 osteoporotic women have had a fracture: Colles, hip or vertebral (spinal deformity index) fracture. VDR were determined by PCR directed to demonstrate the presence (b) or absence (B) of a restriction target for Bsml in intron 7. We analyzed some biochemical markers of bone remodelling: serum levels of alkaline phosphatase, tartrate resistant acid phosphatase and urine ratios of calcium/creatinine and hydroxyproline/creatinine. We also determined calciotropic hormones: parathyroid hormone and calcitonin. Bone mass was measured by DEXA and TC. RESULTS: There were no significant differences in either biochemical bone remodelling markers or in bone mass between the three genotypes: bb, Bb and BB, either in controls or in osteoporotic women with the exception of alkaline phosphatase which had a significative increase compared to control in women with unfavorable alleles distribution (bB and BB). Distribution of genotypes was similar between controls and osteoporotic women, with or without fractures. CONCLUSIONS: In Canarian women, VDR genotype is not associated with changes in biochemical markers of bone remodelling or in bone mass or with the presence of osteoporosis or osteoporotic fractures.

Absorptiometry, Photon↗

Genetic polymorphisms in the Hmong population: implications for cancer etiology and survival.

BACKGROUND: The Hmong, an isolated, agrarian people from southern China, migrated to the mountainous regions of what are today Vietnam, Cambodia, and Laos. Minnesota has the second largest Hmong population in the United States. The authors compared frequencies of common genetic polymorphisms believed to influence risk of malignancy to determine whether frequencies in the Hmong are different from those in other Asian populations and in white Minnesotans. METHODS: Genotyping for glutathione S-transferase micro1 (GSTM1), glutathione S-transferase theta1 (GSTT1), myeloperoxidase (MPO) (C(-)463T), nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase (NQO1) (C609T), 5,10-methylenetetrahydrofolate reductase (MTHFR) (C677T), MTHFR (A1298C), methionine synthase reductase (MTRR) (A66G), X-ray repair cross complementing 1 (XRCC1) 194 (Arg194Trp), XRCC1 280 (Arg280His), and XRCC1 399 (Arg399Gln) alleles was performed by TaqMan analysis using DNA isolated from newborn heel-stick spots provided by the Minnesota Department of Health. RESULTS: The Hmong had significantly higher frequencies of the NQO1 T allele and the XRCC1 Trp polymorphism (Arg194Trp) and had significantly lower frequencies of the G allele in MTRR (A66G) and the T allele in MTHFR (C677T) compared with white Minnesotans. The Hmong also were significantly more likely to lack the GSTM1 and GSTT1 genes compared with whites (82% vs. 54% and 61% vs. 18%, respectively). Genotype frequencies were similar for MTHFR (A1298C), MPO (C(-)463T), and XRCC1 (Arg280His, Arg399Gln). Genotype frequencies at these loci also were compared with those reported for other Asian populations and showed notable differences between the Hmong and Chinese/Taiwanese, Korean, and Japanese populations. CONCLUSIONS: The genetic differences identified have implications for both cancer etiology and prognosis in this unique population.

Asia↗

Genetic polymorphism of human serum ribonuclease I (RNase I).

One of the human urinary ribonucleases (RNases) was isolated and purified to homogeneity (SDS-PAGE) by means of a series of column chromatographies. The enzyme, designated RNase 1, is a glycoprotein with a molecular weight of approximately 16,000. Rabbit antibody to the purified RNase 1 reacted with human urine and sera, as well as with the purified RNase 1. The genetic polymorphism of serum RNase 1 was studied by polyacrylamide gel isoelectric focusing (IEF-PAGE) in a pH range of 5-8, followed by immunoblotting with antisera specific for RNase 1. Two common phenotypes, RNASE1 1 and RNASE1 1-2, were easily recognized. The homogeneous phenotype, RNASE1 1, consisted of four major bands with different pI values, and the heterogeneous phenotype, RNASE1 1-2, was presumed to represent a mixture of each of the homogeneous phenotypes 1 and 2; however, the other homogeneous phenotype, RNASE1 2, was not detected in our samples. Family studies are in agreement with an autosomal codominant transmission of the two alleles. Population studies indicate that the frequencies of the RNASE 1 and RNASE1 2 alleles are .988 and .012, respectively.

Adult↗

Influence of genetic polymorphisms on responsiveness to dietary fat and cholesterol.

Genes influence quantitative variations in plasma lipoprotein concentrations. For example, intake of dietary saturated fat and cholesterol raises the average serum cholesterol concentration, leading to a higher risk of coronary artery disease in populations. However, not all individuals within the population are susceptible: genetic factors appear to render individuals either "dietary responsive" or "dietary nonresponsive." In this review, we focus on current knowledge about the influence of genetic polymorphisms in certain genes on the lipoprotein response to dietary fat and cholesterol. Our preliminary studies in the Dietary Intervention Study in Children suggest a significant dose-response relation between the decrease in LDL cholesterol from baseline to 36 mo of follow-up in both the intervention group (who consumed a low-fat, low-cholesterol diet) and the usual care group (who consumed a regular diet) and the presence of the APOA1*A allele at the M1 site and the + site at the M2 site of the gene encoding apolipoprotein (apo) A-I. The DNA polymorphisms on the genes encoding apo A-IV, apo B, apo C-III, apo E, lipoprotein lipase, cholesteryl ester transfer protein, lecithin:cholesterol acyltransferase (phosphatidylcholine-sterol O:-acyltransferase), and LDL receptor were found by others to be associated with the plasma lipoprotein response to dietary intervention. Possible mechanisms involved in these effects are discussed and certain discrepancies in the literature about some genetic effects on responsiveness are analyzed. An improved understanding of the influence of specific genes on lipoprotein responsiveness to dietary fat and cholesterol may allow us to identify and counsel certain individuals to avoid high-fat diets so that they may reduce their risk of developing hyperlipidemia and coronary artery disease.

Adult↗

Mitochondrial malate dehydrogenase: a new genetic polymorphism in man.

Starch-gel electrophoresis patterns of malate dehydrogenase from human tissue indicate a new genetic polymorphism for the mitochondrial form of the enzyme. Studies of families showed simple Mendelian segregation rather than maternal inheritance, suggesting that not all mitochondrial proteins are coded by mitochondrial DNA.

DNA↗

[Relationship of genetic polymorphism of microsomal epoxide hydrolase with susceptibility of chronic benzene poisoning].

OBJECTIVE: To explore the relationship between genetic polymorphisms of microsomal epoxide hydrolase (mEH) and susceptibility of chronic benzene poisoning (BP). METHOD: A case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. Polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) on c.113 and c.139 of mEH gene. RESULTS: The risk of BP for individuals carrying mEHc.113 C/C genotype was 0.60 (OR = 0.60, 95% CI: 0.37 - 0.97, P = 0.04) of those carrying T/T and T/C genotypes. In non-smoking population, the risk of BP for subjects carrying mEHc.113 C/C genotype was 0.56 (OR = 0.56, 95% CI: 0.33 - 0.96, P = 0.03) of those carrying T/T and T/C genotypes, and in non-drinking population, the individuals carrying mEHc.113 C/C genotype was 0.51 (OR = 0.51, 95% CI: 0.30 - 0.86, P = 0.01) of those carrying T/T and T/C genotypes. CONCLUSION: The subjects carrying mEHc.113 C/C genotype and together with non-smoking or non-drinking habit may have lower risk of chronic benaene poisoning.

Adult↗

Genetic polymorphisms of CYP2D6, GSTM1, and GSTT1 genes and bladder cancer risk in North India.

The study consisted of 100 patients (97 males and 3 females) suffering from bladder cancer and 76 matching controls. The maximum number of patients in this study was in the age group of 61-70 years. The prevalence of genetic polymorphism in the CYP2D6, GSTM1, and GSTT1 genes has been investigated to find their association with risk of bladder cancer. While there was no association between the heterozygous (HEM) genotype of the CYP2D6 gene with the risk of bladder cancer [odds ratio (OR)=1.00; 95% confidence interval (CI)=0.46-2.16], it was 1.5-fold with poor metabolizers (PM) genotype. When stratified according to different grades of bladder cancer, a significant association was found with an OR=3.54 (95% CI=0.89-13.98) in grade II, 3.3 (95% CI=0.12-20.6) in grade III, and 1.67 (95% CI=0.15-18.45) in grade IV. When stratified in relation to smoking status, significant association of the disease was found in heavy smokers with an OR=2.13 (95% CI=0.71-6.43). Subjects with the null genotype for GSTM1 had a slightly significant association with the bladder cancer risk and the risk increased to 2-fold with the GSTT1 null genotype. Smoking status also revealed an impact on the prevalence of bladder cancer in the individuals with GSTM1 and GSTT1 null genotypes. The results indicated that there is a 3-fold increase in risk of developing this cancer in the presence of one copy of the variant CYP2D6 (HEM) allele and null GSTT1.

Aged↗

Impact of genetic polymorphisms in transmembrane carrier-systems on drug and xenobiotic distribution.

Active transport across biological membranes has become a noticeable factor in the absorption, distribution, and excretion of an increasing number of drugs. Different transmembrane transport systems including organic anion transporters (OATP, solute carrier family SLC21A), organic cation transporters (OCT, SLC22A), dipeptide transporters (PEPT, SLC15A), nucleoside transporters (CNT, SLC28A), monocarboxylate carriers (MCT, SLC2A), and members of the large ATP-binding cassette family (ABC, SLC3A) are involved in drug disposition. Genetic polymorphisms in transport proteins frequently occur and contribute to interindividual differences in the efficacy and safety of pharmatherapy. Currently, the most advanced research has been done on P-glycoprotein (ABCB1, SLC3A1.201.1). Knowledge of this transporter indicates that haplotype analysis rather than association with single nucleotide polymorphisms (SNPs) provides the most appropriate interpretation of pharmacogenetic data from drug transporters. This review gives an overview and update on the pharmacological impact of genetic variants in transmembrane transporters.

Animals↗

Genetic polymorphism and linkage disequilibrium of the HLA-DP region in Basques from Navarre (Spain).

In this work, a sample of 116 individuals from an autochthonous Basque population (northern Navarre, Spain) was typed at the DNA level for HLA-DPA1 and HLA-DPB1 loci, with the aim of analysing the genetic polymorphism and the linkage disequilibrium (LD) of the HLA-DP region. In this Basque subpopulation, the most frequent alleles were *0103 (0.767) and *0201 (0.185) for DPA1 locus, whereas for DPB1 locus the *0401 allele was predominant (0.307). Accordingly, the most frequent haplotype was DPA1*0103-DPB1*0401 (0.300), which showed a significant LD. However, the haplotypes that most differentiated the sample of Navarre from other worldwide populations already analysed were DPA1*0105-DPB1*1901 (0.011) and DPA1*0201-DPB1*7601 (0.021), both of which showed a strong LD. Analysis of the relationships between populations based on data provided by HLA-DPA1 and HLA-DPB1 loci revealed a high genetic affinity between the Basque samples (North Navarre and Guipúzcoa), which, in turn, tend to plot separately from the remaining European populations. Gene frequency clines for DPB1*01, DPB1*04 and DPB1*11 alleles among European populations are reported for the first time. These alleles showed maximum values of F(ST) (0.033, 0.034 and 0.025, respectively). Various evolutionary forces were considered in discussing the origin of the spatial structuring of the gene frequencies: (i) gene flow, argued from the hypotheses of Post-glacial recolonization from southern Europe or the demic diffusion of farmers from the Near East into Europe, and (ii) the existence of selective pressures that could have generated genetic microdifferentiation.

Gene Frequency↗

A novel genetic polymorphism of inducible nitric oxide synthase is associated with an increased risk of gastric cancer.

AIM: Inducible nitric oxide synthase (iNOS) plays a central role in the pathway of reactive oxygen and nitrogen species metabolism when Helicobacter pylori (H pylori) infection occurs in humans. iNOS Ser(608)Leu allele, a novel genetic polymorphism (C/T) occurring within exon 16 of the iNOS reductase domain, may have a dramatic effect on the enzymatic activity. The aim of this study was to determine whether iNOS C/T polymorphism was associated with increased susceptibility to gastric cancer. METHODS: We conducted a population based case-control study in a high gastric cancer incidence area, Yangzhong, China. Questionnaires from 93 patients with intestinal type gastric cancer (IGC), 50 with gastric cardia cancer (GCC) and 246 healthy controls were obtained between 1997 and 1998, and iNOS genotyping was carried out. Odds ratios (ORs), interaction index (gamma), and 95% confidence intervals for the combined effects of iNOS genotype and H pylori infection, cigarette smoking or alcohol drinking were estimated. RESULTS: The frequency of (CT+TT) genotypes was higher in cases than in control group (24.48% vs 23.17%), but the difference was not statistically significant. After adjusting for age and gender, past cigarette smokers with (CT+TT) genotypes had a significantly increased risk of IGC (OR = 3.62, 95% CI: 1.23-10.64), while past alcohol drinkers with (CT+TT) genotypes had a significantly increased risk of GCC (OR = 3.33, 95% CI: 1.14-9.67). H pylori CagA negative subjects with (CT+TT) genotypes had a significantly increased risk of both IGC and GCC (OR = 2.19 and 3.52, respectively). CONCLUSION: iNOS Ser(608)Leu allele may be a potential determinant of susceptibility to cigarette -alcohol induced gastric cancer, but larger studies are needed to confirm the observations.

Adult↗

Genetic polymorphisms of the Caucasus ethnic groups: distribution of some blood group genetic markers (Part II).

The compiled data on the distribution of polymorphic blood groups (ABO, Diego, Duffy, Kell-Cellano, Kidd, MN, MNSs, P, Penney, Rh(D), Rh-Hr), secretion ABH antigens in saliva, HLA system (HLA-A, HLA-B, HLA-C, HLA-DR), immunoglobulin (GM1) and other miscellaneous data (phenylthiocarbamide taste, tongue rolling) in the Caucasus are presented. Results of the interpopulation heterogeneity test show that, in spite of the limited territory of the Caucasus, a high level of genetic variability was observed. In terms of gene frequencies, these ethnic groups are approximately equidistant from European and West Asian Populations.

Asia, Western↗

Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus-associated hepatocellular carcinoma.

BACKGROUND: The carcinogenic process can be modulated by exposure to endogenous or environmental substance(s) acting as carcinogens or protocarcinogens. Polymorphic enzymes of cytochrome P450 (CYP) that play a role in detoxication/toxication of such substances via metabolization may account for the interpatient variability of clinical course in cancers such as hepatocellular carcinoma (HCC). Many CYP genetic polymorphisms, which may change enzyme activity, are known to exist in Japanese. The aim of the present study was to compare the frequencies of CYP polymorphisms between hepatitis C virus (HCV)-related HCC patients and healthy subjects. METHODS: Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. These mutant alleles have been reported to change the CYP enzyme activity in Japanese. The frequencies of the mutant alleles and genotypes were then compared with those reported in healthy Japanese. RESULTS AND CONCLUSION: There is no statistically significant difference in genetic mutant alleles between the two groups, except for the genotype of CYP2A6*4A homozygous. The frequency of this genotype in the HCC patients (0.144) is significantly higher than that in healthy Japanese (0.034; P < 0.05; odds ratio 3.36). The clinical significance related to HCC is unknown. Further evaluation of CYP2A6*4A (deletion type) in HCV-related HCC patients is required.

Aged↗

Genetic polymorphism of induction of CYP1A1 (EROD) activity.

CYP1A1 is a cytochrome P450 which is inducible by polycyclic aromatic hydrocarbons (PAH). This induction is mediated via the Ahr locus which encodes the cytosolic Aryl hydrocarbon receptor. The induced activity of CYP1A1 can be measured in vitro by the ethoxyresorufin-O-deethylase (EROD) activity in lymphocytes after induction by benz(a)anthracene (B(a)A). Our purpose was to determine, using this assay, the genetic polymorphism of CYP1A1 induction. With this aim, a population and family study was undertaken. Using the statistical SKUMIX method, a bimodal distribution (two peaks) of the induced EROD activity among 102 unrelated individuals was obtained. We were unable to discriminate three classes of CYP1A1 induction phenotype since a trimodal distribution did not significantly improve the fit to the data (chi 2(1) = 0.37, p > 0.9). Segregation analysis performed on 57 nuclear families gave evidence of a major gene effect together with a polygenic component. The frequency of the high induction allele is equal to 0.11 with dominance on the low induction allele. This is an accordance with two distributions, with individuals showing low and high CYP1A1 induction phenotypes in proportions of 89% and 21% respectively. However, some degree of overlap between the two distributions prevented a clear genotype classification on the basis of the phenotype measured with the EROD assay. Further analyses should not be made with a dichotomized phenotype (low and high inducers) but should use quantitative measurements.

Adolescent↗

Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients with coronary heart disease.

OBJECTIVES: To determine if polymorphisms of the tissue plasminogen activator (t-PA) gene influence acute endogenous t-PA release in patients with coronary heart disease (CHD). METHODS: Forearm blood flow and plasma t-PA concentrations were measured in response to intra-brachial infusion of substance P and sodium nitroprusside in 96 patients with stable CHD. Genotyping was performed using a Taqman polymerase chain reaction assay specifically designed to detect the polymorphisms of interest: (i) Alu-repeat insertion/deletion sequence; (ii) C-->T substitution in an upstream enhancer region (-7351 C/T); (iii) T-->C in exon 6 (20 099 T/C); and (iv) T-->A (27 445 T/A) in intron 10. RESULTS: Substance P and sodium nitroprusside caused dose-dependent increases in forearm blood flow in all patients (P < 0.001 for all) that were independent of the four genetic polymorphisms. Similarly, there were no differences in basal plasma t-PA antigen concentrations or net t-PA release between genotypes. Compared to non-smokers, smokers exhibited impaired substance P-induced vasodilatation (P < 0.001) and t-PA release (P = 0.05). CONCLUSIONS: Despite confirming our previous findings in cigarette smokers, we have found no effect of polymorphisms of the t-PA gene on two complementary aspects of endothelial function. We conclude that genetic variation of the t-PA locus is unlikely to have a major influence on acute t-PA release in subjects with established CHD.

Aged↗