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PubMed2000

Disease, frequency-dependent selection, and genetic polymorphisms: experiments with stripe rust and wheat.

Pathogens have the potential to maintain genetic polymorphisms by creating frequency-dependent selection on their host. This can occur when a rare host genotype is less likely to be attacked by a pathogen (frequency-dependent disease attack) and has higher fitness at low frequency (negative frequency-dependent selection). In this study, we used wheat genotypes that were susceptible to different races of the pathogen Puccinia striiformis to test whether disease created frequency-selection on its host and whether such selection could maintain polymorphisms for resistance genes in the wheat populations. Four different two-way mixtures of wheat genotypes were planted at different frequencies in both the presence and absence of disease. Disease created frequency-dependent selection on its host in some populations. Unknown factors other than disease also created frequency-dependent selection in this system because, in some instances, rare genotype advantage was observed in the absence of disease. Although the pathogen created frequency-dependent selection on its host, this selection was not sufficient to maintain genetic polymorphism in the host populations. In all cases where frequency-dependent selection occurred only in the diseased plots, one of the two genotypes was predicted to dominate in the population and the same genotype was predicted to dominate in both the presence and absence of disease. Only in cases where frequency-dependent selection was not caused by disease was there evidence that genetic polymorphisms would be maintained in the population. The frequency-dependent selection described in this study is a consequence of epidemiological effects of disease and differs from the time-lagged frequency-dependent selection resulting from coevolution between hosts and parasites. The impact of this direct frequency-dependent selection on the maintenance of genetic polymorphisms in the host population is discussed.

Fungi↗
PubMed2004

T102C genetic polymorphism of the 5-HT2A receptor in Chinese hypertensive patients and healthy controls.

1. The 5-HT(2A) receptor belongs to the G-protein superfamily. It plays an important role in vascular regulation. 2. Previous reports in the UK have indicated that there is an association of the T102C genetic polymorphism of the 5-HT(2A) receptor with hypertension, but no studies have been made on the T102C genetic polymorphism in Chinese hypertensive patients. In the present study, we investigated the T102C genetic polymorphism of 5-HT(2A) receptors in Chinese hypertensive patients to determine whether there is an association of this polymorphism with hypertension in Chinese. 3. The present study was conducted on 198 hypertensive patients and 164 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism was used to identify the T102C genetic polymorphism of the 5-HT(2A) receptor. 4. In the present study, the C allele frequency of the 5-HT(2A) receptor genetic polymorphism was 0.343 in hypertensive patients, which was not significantly different to that in healthy controls (0.393; chi(2) = 1.922; P = 0.166; odds ratio = 0.807, 95% confidence interval 0.596-1.093). In addition, no gender differences were observed. 5. In conclusion, to our knowledge, this is the first report on the T102C genetic polymorphism of the 5-HT(2A) receptor in Chinese hypertensive patients. We find that no correlation exists between the T102C genetic polymorphism and hypertension, which affords useful information on the pathogenesis of hypertension in the Chinese population.

Aged↗
PubMed1982

Genetic analysis of human lymphocyte proteins by two-dimensional gel electrophoresis: 4. Genetic polymorphism of cytosol 100k polypeptide.

We describe a genetic polymorphism of a human cellular polypeptide with mol. wt. 100,000, detected in peripheral blood lymphocytes by high resolution two-dimensional electrophoresis. Three different electrophoretic types (1-1, 2-1, and 2-2) of the polypeptide have been identified. Family and population studies indicate that the three phenotypes of the polypeptide are determined by two common alleles at a single autosomal locus. The polypeptide occurs in the cytosol and is one of the abundant polypeptides of B-lymphoblastoid cells, T-lymphoblastoid cells, fibroblasts, and HeLa cells. The data indicate that the cytosol polypeptide with mol. wt. 100,000 shows a genetic polymorphism determined by a new autosomal locus. It is proposed that the polypeptide and its locus be temporarily designated cytosol 100k polypeptide (C100k polypeptide) and C100P, respectively. In a Japanese population, the gene frequencies of C100P1 and C100P2 were 0.907 and 0.093, respectively.

Alleles↗
PubMedDate not supplied

Genetic polymorphisms and susceptibility to esophageal cancer among Chinese population (review).

Esophageal cancer, which is prevalent in China and some other parts of the world, is a complex disease likely resulting from polymorphisms of multiple interacting genes and gene-environment interactions. Recent efforts have been made to analyze the associations between risk of this cancer and hereditary sequence variations in genes involved in metabolism, DNA repair and cell cycle control. We summarized here the results of published case-control studies that have examined the effects of common alleles of 15 genes, MTHFR, CYP1A1, CYP2A6, CYP2E1, GSTM1, GSTT1, GSTP1, NAT2, XRCC1, XPD, hOGG1, MGMT, p53, CNDD1 and L-Myc, on risk of esophageal squamous cell carcinoma among Chinese. Statistically significant differences in genotype frequencies found in case-control comparisons were MTHFR C677T and A1298C polymorphisms, the XRCC1 Arg194Trp polymorphisms, the hOGG1 Ser326Cys polymorphism, and the p53 Arg72Pro polymorphism. The overall effects of these genetic polymorphisms were moderate in terms of relative risk, with ORs ranging from 2-10. There was also some evidence that genetic polymorphisms in certain carcinogen-metabolizing enzymes such as CYP2E1, CYP1A1, CYP2A6, GSTM1, and GSTP1 modulate risk of the cancer, although the results require confirmation with larger sample size studies. For polymorphisms in GSTT1, XPD, CCND1, and L-Myc, the risk estimate from the studies was sufficiently precise to exclude an OR >/=1.5.

Carcinogens↗
PubMed2001

[Genetic polymorphism and cancer].

The clinical pathological significance of genetic polymorphism in cancer is reviewed from the following standpoint. 1) Genetic diagnosis of cancer, especially for loss of heterozygosity 2) Interference with laboratory data: For example, the polymorphisms in secretor and Lewis genes make effect on the serum levels of CA19-9. 3) Cancer susceptibility: Molecular epidemiological studies revealed some genetic polymorphisms were related with cancer susceptibility and were useful for biomarkers of cancer risk. 4) Drug sensitivity: The differences in drug toxicity are sometimes attributed to genetic variability in some enzymes responsible for drug metabolism. When the polymorphisms related with drug degradation were examined, the exact drug would have been selected for each individual. Genetic polymorphisms are strongly related with clinical practice of cancer. After the information about genetic polymorphisms is accumulated, tailor-made medicine(therapy/prevention/diagnosis) will be applicable to medical care of individuals.

Genetic Predisposition to Disease↗
PubMed2005

[Alcohol-induced arterial hypertension and genetic polymorphism of alcohol-metabolizing enzymes].

AIM: To study arterial pressure (AP) and heart rate (HR) in patients suffering from alcohol withdrawal syndrome (AWS) with relation to genetic polymorphism of alcohol dehydrogenase-2 (ADG2) and aldehyde dehydrogenase-2 (AlDG2). MATERIAL AND METHODS: AP and HR were analysed for 36 alcoholics (83 hospitalizations, including repeated ones) with genotypes ADG2 and AIDG2 at admission to and discharge from narcological hospital. RESULTS: ADG2 genotypes distribution was the following: ADG2-1/1--61.1% (n = 22); ADG2-1/2--36.1% (n = 13); ADG2-2/2--2.8% 9n = 1). All the patients had a genotype AIDG2-1/1. A hypertensive reaction occurred in 75.9% inpatients with AWS. At admission, patients with genotype ADG2-1/1 had significantly higher systolic AP and HR vs those with allele ADG2-2: 146.6 +/- 17.0 mmHg against 141.2 +/- 14.9 mmHg, 95.6 +/- 13.9 b/min vs 88.5 +/- 12.2 b/min, respectively. In homozygous genotype ADG2-1/1 AP and HR were higher than in heterozygotes: SAP 152.3 +/- 12.9 mm Hg vs 145.2 +/- 16.2 mm Hg, pulse pressure 57.2 +/- 11.9 vs 50.0 +/- 15.1 mm Hg, HR 96.8 +/- 13.4 b/min vs 87.7 +/- 12.0 b/min. The groups had similar mean diastolic pressure. At discharge, AWS standard therapy resulted in a significant lowering of AP and HR in the study group. Mean values of the parameters in groups with different genotypes did not differe at discharge. CONCLUSION: Population of alcoholics from the Moscow Region had allele polymorphism ADG2. Genetic polymorphism AlDG2 is not typical for this group. Hypertensive reaction was registered in the majority of alcoholics in AWS. Higher systolic, pulse pressure and heart rate were significantly higher in the AWS group with genotype ADG2-1/1. Controlled alcohol withdrawal entails a significant reduction of AP and HR.

Adult↗
PubMed2005

Association of genetic polymorphisms of MK, IL-4, p16, p21, p53 genes and human gastric cancer in Taiwan.

AIMS: To assess gastric cancer risk and clinical-pathological factors associated with genetic polymorphisms of MK, IL-4, p16, p21 and p53 genes. METHODS: A retrospective study was conducted for 123 patients who had recently developed primary gastric cancer. Clinical data and pathological findings were collected, genetic polymorphisms of MK, IL-4, p16, p21 and p53 genes were analysed, and the associations of genetic polymorphisms with gastric cancer carcinogenesis were evaluated. RESULTS: There was significant association of genetic polymorphisms between gastric cancer and control groups in p53 genes. After further stratification of the cancer group into different clinical-pathologic parameters, there were significant associations in the sex and LN involvement groups in MK gene; alcohol consumption group in p16 gene; age and cell differentiation groups in p21 gene; age and tumour location groups in p53 gene; but we fail to find any significant association with IL-4 gene polymorphisms. CONCLUSIONS: Genetic susceptibility testing is a tool to evaluate the association of genetic polymorphisms with gastric cancer carcinogenesis.

Adult↗
PubMed1991

[Genetic polymorphism of the metabolism of drugs used in cardiac diseases].

The genetic determinants of the metabolism of certain drugs used in cardiology is one predictable cause of variability in their pharmacokinetics and effects. Genetic polymorphism of the metabolism of drugs is characterised by the existence of several metabolic phenotypes, usually 2, which allow distinction between fast and slow metabolisers. Clinical identification of these phenotypes is relatively simple. The enzymatic deficiency in slow metabolisers concerns a specific metabolic pathway responsible for the biotransformation of the drug but it respects other eventual metabolic pathways. For a given drug and a given metabolic pathway, slow metabolisers are unable to eliminate the parent product by hepatic metabolism. When the drug is given orally, the plasma concentrations of the parent product in slow metabolisers are 5 to 25 times higher than those observed in fast metabolisers. Depending on the given drug, doses usually well tolerated by fast metabolisers may cause excessive effects in slow metabolisers. The pharmacodynamic consequences of genetic polymorphism on the metabolism of drugs depend essentially on the therapeutic index of the drug concerned and on the activity of the metabolites formed by the genetically determined pathway of the parent product. The pharmacokinetic and pharmacodynamic consequences of the two main genetic polymorphisms concerning drugs used in cardiology are discussed: the polymorphism of N acetylation and that of cytochrome P-450 IID6.

Acetyltransferases↗
PubMed2003

[Effects of genetic polymorphisms of ethanol-metabolizing enzymes on alcohol drinking behaviors].

BACKGROUND/AIMS: Genetic variations of ethanol-metabolizing enzymes can affect alcohol drinking behavior. The aims of this study were to investigate and compare the distributions of these genetic polymorphisms between a healthy control group and a heavy drinker group which included an alcoholic liver cirrhosis group. METHODS: Genotypes of ADH2, ALDH2, CYP2E1, and catalase were identified by polymerase chain reaction and restriction fragment length polymorphism. Genomic DNA was extracted from peripheral leukocytes in 42 healthy controls, 12 heavy drinkers, and 30 alcoholic liver cirrhosis patients. RESULTS: 1) The genotype frequencies of ALDH2 (1*1), ADH2 (1*1), CYP2E1 (c1c1), and catalase1 (TT) were 69%, 55%, 38%, and 12%, respectively in healthy Korean males. 2) There was a significant difference in the distribution of the genetic polymorphism of ALDH2 between the control group and heavy drinker group (12 heavy drinkers and 30 alcoholic liver cirrhosis patients). The genotype frequency of ALDH2 mutant, ALDH2 (1*2) and ALDH2 (2*2) in the heavy drinker group (12%) was significantly lower than that in the control group (30%). 3) We didn't find anyone with ALDH2 homozygote mutant (DD) in the heavy drinker group. 4) There was no significant difference in the distribution of genetic polymorphisms in ADH2, CYP2E1 and catalase1 between the two groups. CONCLUSIONS: These results suggest that the absence of ALDH2 mutant genotype is strongly related to heavy drinking behavior. We can not prove, however, any evidence that the polymorphisms of other ethanol-metabolizing enzymes are associated with the determination of alcohol-drinking behavior.

Adult↗
PubMed2004

[Relationship between susceptibility and prognosis of laryngeal cancer and genetic polymorphisms in CYP1A1 and GSTM1].

OBJECTIVE: To investigate the relationship between susceptibility and prognosis of laryngeal cancer and genetic polymorphisms in CYP1A1 GSTM1. METHODS: The genetic polymorphisms of CYP1A1 exon-7 and GSTM1 were analyzed by polymorphism-polymerase chain reaction (PCR) technique in peripheral blood leukocytes of 89 laryngeal cancer cases and 164 non-cancer controls. RESULTS: Either in the frequency of CYP1A1 (W, MW, M) and GSTM1 negative individual of laryngeal cancer were significantly higher than that in the controls(P < 0.05). Combined genetype of CYP1A1 and GSTM1, that is CYP1A1 W/GSTM1 (-), CYP1A1 MW/GSTM1 (-), CYP1A1 M/GSTM1 (+), CYP1A1 M/GSTM1 (-) had higher risk than those combined genotypes, which ratios were 1.42 (0.62-3.22), 1.67 (0.7-4.03), 2.55 (1.0-6.54) and 4.02 (1.65-9.79), respectively. Statistic analysis suggested an interaction between smoking and CYP1A1 M/GSTM1 (-) genotypes polymorphisms which increase risk of laryngeal cancer. There was no significant difference in the frequency of CYP1A1, GSTM1 individual with the development and prognosis of laryngeal cancer. CONCLUSION: The present datas suggested that genetic polymorphisms of CYP1A1 and GSTM1 were susceptible to laryngeal cancer. Individuals with CYP1A1 M or GSTM1 (-) had increased risk of developing laryngeal cancer, but individuals with combined CYP1A1 M/GSTM1 (-) and smoking were more susceptible. Genetic polymorphisms of CYP1A1 and GSTM1 are not related with clinic process of laryngeal cancer.

Carcinoma, Squamous Cell↗
PubMed1990

Genetic polymorphisms of drug metabolism.

The molecular mechanisms of 3 genetic polymorphisms of drug metabolism have been studied at the level of enzyme activity, enzyme protein and RNA/DNA. As regards debrisoquine/sparteine polymorphism, cytochrome P-450IID6 was absent in livers of poor metabolizers; aberrant splicing of premRNA of P-450IID6 may be responsible for this. Moreover, 3 mutant alleles of the P-450IID6 locus on chromosome 22 associated with the poor metabolizer phenotype were identified by Southern analysis of leucocyte DNA. The presence of 2 identified mutant alleles allowed the prediction of the phenotype in approximately 25% of poor metabolizers. The additional gene-inactivating mutations which are operative in the remainder of poor metabolizers are now being studied. Regarding mephenytoin polymorphism, although the deficient reaction, S-mephenytoin 4'-hydroxylation, has been well defined in human liver microsomes, the mechanism of this polymorphism remains unclear. All antibodies prepared to date against cytochrome P-450 fractions with this activity recognize several structurally similar enzymes and several cDNAs related to these enzymes have been isolated and expressed in heterologous systems. However, which isozyme is affected by this polymorphism is not known. As regards N-acetylation polymorphism, N-acetyltransferases have been purified from human liver, specific antibodies prepared; it was observed that immunoreactive N-acetyltransferase is decreased or undetectable in liver of "slow acetylators". Two genes that encode functional N-acetyltransferase were characterized. The product of one of these genes has identical activity and characteristics as the polymorphic liver enzyme. Cloned DNA from rapid and slow acetylator individuals has been analyzed to identify the structural or regulatory defect that causes deficient N-acetyltransferase.

Acetylation↗
PubMed2005

MDR1 genetic polymorphisms and comparison of MDR1 haplotype profiles in Korean and Vietnamese populations.

Two representative genetic variants of the MDR1 gene, 3435C>T and 2677G>T/A, show wide interethnic differences in its genetic polymorphism. In this study, the authors evaluated the genetic polymorphisms of MDR1 and directly compared MDR1 haplotype profiles of the Korean and Vietnamese populations. The 3435C>T and 2677G>T/A variations were analyzed in 632 Koreans and 142 Vietnamese using pyrosequencing. The allelic frequencies of 3435C>T did not significantly differ between the Korean (39.3%) and Vietnamese (36.6%) groups. However, the frequencies of mutant alleles at 2677 locus (T or A allele) showed a significant difference between Koreans (56.2%) and Vietnamese (41.9%), as the frequency of 2677A allele in the Korean subjects (17.1%) was much higher than that of the Vietnamese subjects (6.3%). Linkage analysis revealed that 2677A allele is closely linked to 3435C allele. The frequency of 2677A-3435C haplotype in Koreans was 15.4%, which was significantly higher than that found in Vietnamese subjects (6.3%). In conclusion, the frequencies of MDR1 variants and haplotype profiles showed significant differences between the Korean and Vietnamese populations, especially with respect to the 2677G>T/A variants. Because the 2677A allele was recently found to be functional in vivo and was detected at a high frequency in Koreans, the genotyping of this variant is necessary for pharmacogenetic studies of MDR1 in this population. In addition, by virtue of strong linkage disequilibrium, 2677A-3435C haplotype may help improve the predictability of MDR1 genetic polymorphism for MDR1 functional changes.

Alleles↗
PubMed1999

Effects of genetic polymorphism on ex vivo and in vivo function of beta2-adrenoceptors in asthmatic patients.

BACKGROUND: Genetic polymorphism determines agonist-induced down-regulation and desensitization of beta2-adrenoceptors. OBJECTIVES: The aim of the present study was to investigate the effects of genetic polymorphism on ex vivo (lymphocytes) and in vivo (bronchoprotection) function of beta2-adrenoceptors in asthmatic patients, having been washed out of previous beta2-agonist exposure. METHODS: Sixty patients with stable mild-to-moderate asthma were evaluated, with a post hoc analysis of genotype performed at end of study. Having withheld treatment with long-acting beta2-agonists for > or = 48 h and short-acting beta2-agonists for > or = 12 h, measurements of lymphocyte beta2-adrenoceptors were made for binding density, binding affinity, basal cyclic adenosine monophosphate (cAMP), and maximal cAMP response to isoproterenol (Emax). In addition, in 48 of these patients who were methacholine responsive (PD20 < 1,000 microg), the acute protective effect of formoterol as a 24-microg single dose (at 1 h) was also evaluated. Comparisons were made according to homozygous and heterozygous (Het) polymorphisms at codon 16 and codon 27. RESULTS: There were no significant differences in age, FEV1 percent predicted, or inhaled corticosteroid dose, when comparing mean values for polymorphisms at either codon-16 or codon 27. There were also no significant differences between polymorphisms for any of the measured lymphocyte beta2-adrenoceptor parameters apart from basal cAMP between Glu-27 and Het-27. Mean values for Emax (after-before isoproterenol as pmol/10(6) cells) were as follows: Gly-16 (3.4), Arg-16 (3.5), Het-16 (4.0), Glu-27 (3.9), Gln-27 (3.5), and Het-27 (3.7). Polylorphism had no significant effect on formoterol protection as doubling dose shift in methacholine PD20 (geometric mean): Gly-16 (5.3), Arg-16 (5.4), Het-16 (4.6), Glu-27 (5.3), Gln-27 (5.3), Het-27 (4.5). CONCLUSIONS: Our results show that genetic polymorphism at codon 16 or 27 does not influence stimulated coupling of lymphocyte beta2-adrenoceptors and similarly did not influence the degree of functional antagonism exhibited by formoterol. Thus, a single dose of beta2-agonist when used on demand affords equal protection against bronchoprotection regardless of genetic polymorphism.

Adenylyl Cyclases↗
PubMedDate not supplied

Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung cancer risk.

Genetic polymorphisms of the genes encoding for the xenobiotic metabolizing enzymes result in individual variations in the efficiency of detoxification of environmental carcinogens, and have been extensively associated with variable risk for lung neoplasms in different ethnic and environmental backgrounds. In this study, using PCR-RFLP based assays, we investigated the distribution of genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in Greek lung cancer patients (N=122) and healthy controls (N=178). The frequency of CYP1A1 m1 homozygous genotype was 0.04 in patients and 0.02 in controls (detected in 4.10% of patients and in 1.69% of controls, respectively), that of GSTM1 null genotype was 0.52 in patients and 0.54 in controls, whereas those of GSTT1 null genotype was 0.17 and 0.11, in patients and controls, respectively. The GSTM1 null genotype was more frequent in adenocarcinoma, as well as in lung cancer patients with history of chronic obstructive pulmonary disease (COPD). The GSTT1 null genotype correlated with advanced age of the patients at the time of diagnosis. Three combinations of rare genotypes - in subjects carrying simultaneously deviations from the common genotype in more than one gene - were over-represented in lung cancer patients, compared to control population, and were furthermore significantly associated with history of heavy tobacco consumption in lung cancer patients. The results imply involvement of specific genotype combinations of CYP1A1, GSTM1 and GSTT1 alleles in the development of lung cancer in heavy smokers.

Adenocarcinoma↗
PubMed2004

Genetic polymorphism of the accessory gene regulator (agr) locus in Staphylococcus epidermidis and its association with pathogenicity.

Staphylococcus epidermidis has become one of the most important causes of nosocomial infections in recent years. The staphylococcal accessory gene regulator (agr) is the most important locus responsible for the regulation of virulence factors, and it has been shown to be polymorphic. The aim of this study was to investigate the agr locus and its genetic polymorphisms in different Chinese S. epidermidis isolates and the relationship between genetic polymorphisms and pathogenicity. Specific PCR was used to amplify the different agr groups. Results were confirmed by restriction enzyme digestion and sequence analysis. agr mutations were detected and three agr groups of S. epidermidis were determined. Of the isolates, 12 % were pathogenic S. epidermidis and 17 % had naturally occurring agr mutations (P > 0.05). Pathogenic S. epidermidis isolates comprised 68.2 % agr group I, 19.3 % group II and 12.5 % group III, while isolates from healthy controls comprised 39 % agr group I, 51 % group II and 10 % group III (P < 0.01). The percentages of agr locus mutants and the three agr groups in different hospitals showed no significant differences (P > 0.05). The percentage of agr group I S. epidermidis isolated from catheters and blood was higher than that isolated from the other clinical specimens. This is the first study to investigate the genetic polymorphism of agr in S. epidermidis in China. The mean percentage of agr locus mutants was 14.9 % (12 % in clinical specimens; 17.7 % in controls). Genetic polymorphism of agr in S. epidermidis was linked to its pathogenicity; group I was associated with pathogenicity, while most isolates from healthy subjects were group II. The mechanism is to be investigated.

Bacterial Proteins↗
PubMed2006

Genetic polymorphisms of the uridine diphosphate glucuronosyltransferase 1A7 and colorectal cancer risk in relation to cigarette smoking and alcohol drinking in a Chinese population.

BACKGROUND: The impact of uridine diphosphate glucuronosyltransferase 1A7 (UGT1A7) polymorphisms on genetic susceptibility to digestive system cancer has received close attention since the discovery by Guillemette, the polymorphisms of which may alter enzyme activity. To clarify the allele frequency distribution and its association with risk of colorectal cancer, a population-based case-control study was carried out in Chinese population. METHODS: A total of 140 patients with colorectal cancer and 280 cancer-free frequency-matched controls from a follow-up cohort population established in 1989, were enrolled. For the UGT1A7 polymorphisms analysis, polymerase chain reaction (PCR)-based genotyping techniques including semi-nested PCR, allele-specific PCR and PCR-restriction fragment length polymorphism (RFLP) were developed. RESULTS: The variant allele frequencies in patients and controls were 50.0% and 38.6%, respectively, which were significantly associated with risk of colorectal cancer (odds ratio [OR]: 1.59; 95% confidence interval [CI]: 1.19-2.13). For the variant genotypes analysis, *2/*2 and *3/*3 exhibited a significant association with risk of colorectal cancer (OR: 7.80, 95%CI: 2.66-22.87; OR: 3.47, 95%CI: 1.51-7.97, respectively). Stratification analysis indicated that in previous-current cigarette smoking (cigarette smoking history), current cigarette smoking (current cigarette smoking status), previous-current alcohol drinking (alcohol drinking history) or current alcohol drinking individuals (current alcohol drinking status), the risk developing colorectal cancer increased: OR (95%CI), 2.81 (0.97-8.11), 3.39 (1.19-9.67), 2.89 (0.99-8.46) and 3.14 (1.09-9.09), respectively. CONCLUSIONS: UGT1A7 polymorphisms may have a significant modifying effect on colorectal cancer risk, which may interact with environmental factors, cigarette smoking and alcohol drinking in colorectal carcinogenesis.

Aged↗
PubMedDate not supplied

[The genetic polymorphism of somatotropin].

This review deals with the growth hormone genetic polymorphism and presents information about somatotropin variants, which are synthesized in the pituitary gland and in the placenta. The detailed results of somatotropin DNA polymorphism study in different animal species are presented. It is supposed that some DNA alleles which find their source in replacements in non-coding part of the gene, express their phenotype by the deviations in the expression control. The polymorphous somatotropin genetic system may be used as the marker system in the QTL study.

Animals↗
PubMed2002

Population distribution of aldehyde dehydrogenase-2 genetic polymorphism: implications for risk assessment.

The role of genetic polymorphisms in modulating xenobiotic metabolism and susceptibility to cancer and other health effects has been suggested in numerous studies. However, risk assessments have generally not used this information to characterize population variability or adjust risks for susceptible subgroups. This paper focuses upon the aldehyde dehydrogenase-2 (ALDH2) system because it exemplifies the pivotal role genetic polymorphisms can play in determining enzyme function and susceptibility. Allelic variants in ALDH2 cause decreased ability to clear acetaldehyde and other aldehyde substrates, with homozygous variants (ALDH2*2/2) having no activity and heterozygotes (ALDH2*1/2) having intermediate activity relative to the predominant wild type (ALDH2*1/1). These polymorphisms are associated with increased buildup of acetaldehyde following ethanol ingestion and increased immediate symptoms (flushing syndrome) and long-term cancer risks. We have used Monte Carlo simulation to characterize the population distribution of ALDH2 allelic variants and inter-individual variability in aldehyde internal dose. The nonfunctional allele is rare in most populations, but is common in Asians such that 40% are heterozygotes and 5% are homozygote variants. The ratio of the 95th or 99th percentiles of the Asian population compared to the median of the U.S. population is 14- to 26-fold, a variability factor that is larger than the default pharmacokinetic uncertainty factor (3.2-fold) commonly used in risk assessment. Approaches are described for using ALDH2 population distributions in physiologically based pharmacokinetic-Monte Carlo refinements of risk assessments for xenobiotics which are metabolized to aldehyde intermediates (e.g., ethanol, toluene, ethylene glycol monomethyl ether).

Aldehyde Dehydrogenase↗