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At least 1,531 records · Page 85Linked to original sources
PubMed2005

Genetic polymorphism in the phenobarbital-responsive enhancer module of the UDP-glucuronosyltransferase 1A1 gene and irinotecan toxicity.

Genetic polymorphism of the UDP-glucuronosyltransferase (UGT) 1A1 gene is associated with the decreased glucuronidation activity of an active metabolite of irinotecan, SN-38, and UGT1A1*28 has been shown as a predictive factor for irinotecan toxicity. The phenobarbital-responsive enhancer module (PBREM) of the UGT1A1 promoter region has been reportedly associated with the transcriptional activity of the gene. We investigated whether the polymorphism of PBREM (T-3279G) would affect inter-patient variations in sensitivity to irinotecan toxicity. The study population comprised 119 cancer patients who had received irinotecan. We reviewed their clinical records, including patient characteristics, and observed their toxicity levels following irinotecan infusion. Genotyping was performed by sequencing analyses. Logistic regression analyses were performed to assess the relationship between genotypes and irinotecan toxicity. We identified the homozygotes of the reference allele for T-3279G in 68 patients, the heterozygotes in 37, and the homozygotes for the variant in 14. Logistic regression analysis indicated a significant association between the homozygotes for T-3279G and the severe toxicity (odds ratio 5.80; 95% confidence interval 1.67-20.1). However, multivariate analysis, including the data of UGT1A1*28 polymorphism, revealed a diminution of the association due to a highly significant linkage disequilibrium between these polymorphisms. Our results suggest that a highly significant linkage disequilibrium exists between T-3279G and UGT1A1*28 polymorphisms, and that the variants of T-3279G and UGT1A1*28 cooperatively decrease transcriptional activity of the UGT1A1 promoter. The determination of T-3279G and UGT1A1*28 genotypes might be clinically useful in predicting severe irinotecan toxicity in cancer patients.

Adult↗
PubMed2006

In vivo evaluation of coumarin and nicotine as probe drugs to predict the metabolic capacity of CYP2A6 due to genetic polymorphism in Thais.

The association between the distribution characteristics of CYP2A6 catalytic activities toward nicotine and coumarin, and the frequency distribution of CYP2A6 variant alleles reported was estimated in 120 healthy Thais. The distributions of the subjects as classified by the amounts of 7-hydroxycoumarin (7-OHC) excreted in the urine and by cotinine/nicotine ratio in the plasma were clearly bimodal. However, the numbers of apparently poor metabolizers for coumarin and nicotine were different. The inter-individual variability in the in vivo dispositions of coumarin and nicotine closely related to the CYP2A6 genetic polymorphism. There was a close correlation between the rate of 7-OHC excretion in the urine and cotinine/nicotine ratio in the plasma among subjects (R=0.92, p<0.001). The frequency of CYP2A6 allele found in the present study was: CYP2A6*1A=32% (95% CI, 22.1-39.4%), CYP2A6*1B=27% (95% CI, 19.4-33.5%), CYP2A6*9=20% (95% CI, 17.6-23.3%), CYP2A6*4=14% (95% CI, 9.6-17.8%), CYP2A6*7=5% (95% CI, 3.7-9.4%), CYP2A6*10=2% (95% CI, 0.8-5.1%). Subjects having CYP2A6*1A/*1B were found to have a higher rate of 7-OHC excretion, as well as a higher cotinine/nicotine ratio in the plasma compared with those of the other genotypes. In contrast, subjects with CYP2A6*4/*7 and CYP2A6*7/*7 almost lacked any cotinine formation, whereas urinary 7-OHC was still detectable. CYP2A6*9 allele clearly resulted in reduced enzyme activities. Despite the absence of the homozygote for CYP2A6*10 allele, the presence of CYP2A6*10 allele significantly decreased the enzyme activities. The results of the present study demonstrate that in vivo phenotyping of CYP2A6 using nicotine and coumarin are not metabolically equivalent. Nicotine is a better probe according to its specificity, while coumarin is still valuable to be used for a routine CYP2A6 phenotyping since the test employs a non-invasive method.

Administration, Oral↗
PubMed2006

Absence of association between two insertion/deletion coding genetic polymorphisms of TIM-1 gene and asthma in Chinese Han population.

TIM-1, a member of T-cell immunoglobulin domain and mucin domain (TIM) gene family, was implicated as an asthma susceptibility gene in previous studies. TIM-1 was expressed on CD4(+) T cells after activation and its expression was sustained preferentially in T-helper type 2 (T(H)2) but not in T(H)1 cells, therefore TIM-1 became a good candidate gene for atopic diseases. Recent studies indicated that two insertion/deletion (ins/del) coding genetic polymorphisms in exon 4 of TIM-1 were associated with asthma susceptibility in some but not in all populations. In order to investigate the relationship between TIM-1 genetic polymorphisms and asthma in Chinese Han population, we performed a case-control study for two insertion/deletion polymorphisms in TIM-1 exon 4 (5383_5397ins/del and 5509_5511delCAA) and a single nucleotide polymorphism (SNP) in intron 8 (IVS 8+9 G/A) between a healthy control group of 309 people and an asthma patient group of 352 people recruited from Chinese Han population. The polymorphisms were genotyped and the allele and genotype frequencies were analysed, but none of the three polymorphisms showed association with asthma susceptibility in single-locus association analyses. Linkage disequilibrium (LD) analyses demonstrated that the two insertion/deletion polymorphisms were in strong LD but the haplotypes constructed from these two polymorphisms showed no significant association with asthma. In conclusion, our findings suggest that 5383_5397ins/del, 5509_5511delCAA and SNP IVS 8+9 G/A polymorphisms are not associated with asthma susceptibility in Chinese Han population.

Adult↗
PubMed2003

Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma.

The effect of genetic polymorphisms for glutathione S-transferase ( GST) M1, GSTT1, GSTP1-1( GSTP1), cytochrome P450 2E1 ( CYP2E1) and aldehyde dehydrogenase 2 ( ALDH2) on the risk of hepatocellular carcinoma (HCC) was observed in 78 Japanese patients with HCC and 138 non-cancer hospital controls. We found a positive association between cumulative amounts of alcohol consumption (>/=600,000 ml in a lifetime) and the risk of HCC (OR=4.52, 95% CI 2.39-8.55). However, cigarette smoking was not significantly related to the risk of HCC (OR=1.23, 95% CI 0.57-2.68). The allelic frequencies of GSTM1, GSTT1, GSTP1, CYP2E1and ALDH2of HCC patients were not significantly different from those of controls when odds ratios were only adjusted for age and gender except for any 2 alleles of ALDH2in drinkers (OR=2.53, 95% CI 1.21-5.31). However, the frequency of any C2 alleles of CYP2E1and any 2 alleles of ALDH2were significantly higher than those of controls (OR=5.77, 95% CI 1.24-27.39, OR=9.77, 95% CI 1.63-58.60) when covariates including viremia were selected by using stepwise logistic regression analysis. We conclude that habitual alcohol drinking is likely to lead to an increased risk of HCC, and any C2alleles of CYP2E1as well as any two alleles of ALDH2were also associated with an increased risk of HCC.

Adult↗
PubMed2003

Genetic polymorphisms of steroid hormone metabolizing enzymes and risk of liver cancer in hepatitis C-infected patients.

BACKGROUND/AIMS: Genetic polymorphisms of enzymes involved in hormone metabolism can influence hormonal activities and risk of hormone-dependent cancers. As progression of chronic hepatitis C and risk of liver cancer is higher in males than in females, we evaluated whether the polymorphisms of three enzymes participating in the pathway of estrogen and androgen biosynthesis and inactivation, 5alpha-reductase type II (SRD5A2), cytochrome P450c17alpha (CYP17) and catechol-O-methyltransferase (COMT), might affect the expression of hepatitis C virus (HCV)-related liver disease. METHODS: The study included 78 healthy subjects and 387 HCV patients: 100 asymptomatic carriers, 105 hepatitis, 90 cirrhosis and 92 hepatocellular carcinomas (HCC). Variant positions SRD5A2 V89L and A49T, CYP17 (-34)T/C and COMT V108M were analysed by polymerase chain reaction and restriction fragment length polymorphism. A cross-sectional study of association was performed, considering carriers as reference category. RESULTS: The CYP17 (-34)C/C genotype was over-represented in HCC patients as compared to carriers (22.5 vs. 11.2%, odds ratio (OR): 2.29, P: 0.05). Females mostly contributed to this association (OR: 4.95, P: 0.01) and OR values increased in post-menopausal women (OR: 6.00, P: 0.03). No differences were observed for SRD5A2 and COMT gene polymorphisms. CONCLUSIONS: CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

Host genetic polymorphism analysis in cervical cancer.

BACKGROUND: The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals. METHODS: Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA. RESULTS: The tumor necrosis factor-alpha (TNFalpha) -238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.11-0.96], as was the TNFalpha -376 polymorphism (P = 0.02; 0% for any variant genotype in cases vs 4.7% in controls). The NRAMP1 3' untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95% CI, 0.32-1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95% CI, 0.14-1.63; homozygotes, OR = 0.35; 95% CI, 0.11-1.17). The remaining alleles tested showed no association with cervical cancer. CONCLUSIONS: We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFalpha single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.

Cation Transport Proteins↗
PubMed1997

Genetic polymorphisms in human drug metabolic enzymes.

Results obtained from both epidemiologic studies and experimental animal model systems have shown a wide range of phenotypic variation in the ability of individuals to metabolize drugs and environmental chemicals. Several studies have noted correlations between specific metabolic phenotypes and the incidence of disease, suggesting that certain allelic forms of drug metabolic enzymes can render the individual either more sensitive or resistant to the toxic or therapeutic effects of exogenous drugs and chemicals. While some of this variation can be attributed to different environmental exposures, it has become clear that genetic factors also play an important role in determining the response of the individual organism to exogenous agents. Recent advances in molecular biological techniques have begun to allow scientists to correlate observed phenotypic differences with the actual differences in genetic sequence at the gene level. This has allowed a correlation between gene structure and function, thus providing a mechanistic basis to explain the interaction between genetic background and individual response to environmental exposures. Results presented at this symposium discussed how genetic polymorphisms for both Phase I and Phase II metabolic enzymes in the human population modulate the response to environmental toxicants.

Humans↗
PubMed2001

Specificity and genetic polymorphism of the Bacillus competence quorum-sensing system.

A quorum-sensing mechanism involving the pheromone ComX and the ComP-ComA two-component system controls natural competence in Bacillus subtilis. ComX is expressed as a cytoplasmic inactive precursor that is released into the extracellular medium as a cleaved, modified decapeptide. This process requires the product of comQ. In the presence of ComX, the membrane-localized ComP histidine kinase activates the response regulator ComA. We compared the sequences of the quorum-sensing genes from four closely related bacilli, and we report extensive genetic polymorphism extending through comQ, comX, and the 5' two-thirds of comP. This part of ComP encodes the membrane-localized and linker domains of the sensor protein. We also determined the sequences of the comX genes of four additional wild-type bacilli and tested the in vivo activities of all eight pheromones on isogenic strains containing four different ComP receptor proteins. A striking pattern of specificity was discovered, providing strong evidence that the pheromone contacts ComP directly. Furthermore, we show that coexpression of comQ and comX in Escherichia coli leads to the production of active pheromone in the medium, demonstrating that comQ is the only dedicated protein required for the processing, modification, and release of active competence pheromone. Some of the implications of these findings for the evolution and the mechanism of the quorum-sensing system are discussed.

Amino Acid Sequence↗
PubMed1981

Genetic polymorphism of PIF (parotid isoelectric focusing variant) proteins with linkage to the PPP (parotid proline-rich protein) gene complex.

Genetic polymorphism is found among the PIF (parotid isoelectric focusing variant) salivary proteins after separation by prolonged isoelectric focusing in pH 3.5-5.2 urea polyacrylamide slab gels subsequently stained for protein. Two PIF proteins are either present (PIF+) or absent (PIF-) from all salivas. The phenotypes are determined by autosomal inheritance of two alleles, PIF+ and PIF-. Gene frequencies in randomly collected samples show marked racial differences: among 148 whites, PIF+ is 0.66 and PIF- is 0.34; among 90 blacks, PIF+ is 0.35 and PIF- is 0.65; among 78 Chinese, PIF+ is 0.56 and PIF- is 0.44. Studies in 41 families including 129 children support the interpretation of control of PIF by a single autosomal locus. In 8 PIF+ X PIF- matings, there were 8 PIF- (6.34 expected) children. In 33 PIF+ X PIF+ matings, there were 7 PIF- (6.70 expected) children. Linkage studies indicate that PIF is closely linked to the proline-rich protein (PPP) gene complex (e.g., for six families, lod score at theta = 0.00 of PIF/Gl is 3.58). In 107 randomly collected samples from whites, PIF is strongly associated with Db (chi 2(1) = 20.02; P less than 0.0001) and Gl (chi 2(1) = 12.58; P = 0.0005) but not with Pr, Ps, Pm, and Pa proteins. These data (probably reflecting genetic disequilibrium) suggest that PIF may be closer to Db and Gl than to other identified loci of the PPP gene complex. The PPP gene complex includes at least seven genes (and probably more) that produce many acidic and basic proline-rich proteins, constituting about two-thirds of parotid salivary proteins that are thought to have important functions at the tooth surfaces.

Adult↗
PubMed2003

Interactions between genetic polymorphism of cytochrome P450-1B1, sulfotransferase 1A1, catechol-o-methyltransferase and tobacco exposure in breast cancer risk.

Genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and estrogens might play a role in breast carcinogenesis related to environmental exposures. In a case-only study on 282 women with breast cancer, we studied the interaction effects (ORi) between smoking habits and the gene polymorphisms of Cytochrome P450 1B1 (Val432Leu CYP1B1), Phenol-sulfotransferase 1A1 (Arg213His SULT1A1) and Catechol-O-methyltransferase (Val158Met COMT). The smokers carrying the Val CYP1B1 allele associated with a high hydroxylation activity had a higher risk of breast cancer than never smokers with the Leu/Leu genotype (ORi=2.32, 95%CI: 1.00-5.38). Also, the smokers carrying the His SULT1A1 allele associated with a low sulfation activity had a 2-fold excess risk compared to never smokers carrying Arg/Arg SULT1A1 common genotype (ORi= 2.55, 95%CI: 1.21-5.36). The His SULT1A1 allele increased the risk only in premenopausal patients. The Met COMT allele with a lower methylation activity than Val COMT did not modify the risk among smokers. The excess risk due to joint effect could result from a higher exposure to activated tobacco-compounds for women homo/heterozygous for the Val CYP1B1 allele. Also, a lower sulfation of the tobacco carcinogens among women with His SULT1A1 could increase exposure to genotoxic compounds. Alternatively, the Val CYP1B1 or His SULT1A1 allele with modified ability to metabolize estrogens could increase the level of genotoxic catechol estrogen (i.e., 4-hydroxy-estradiol) among smokers. Our study showed that gene polymorphisms of CYP1B1 and SULT1A1 induce an individual susceptibility to breast cancer among current smokers.

Adult↗
PubMed2000

NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase that is involved in chemoprotection and can also bioactivate certain antitumor quinones. This review focuses on detoxification reactions catalyzed by NQO1 and its role in antioxidant defense via the generation of antioxidant forms of ubiquinone and vitamin E. Bioactivation reactions catalyzed by NQO1 are also summarized and the development of new antitumor agents for the therapy of solid tumors with marked NQO1 content is reviewed. NQO1 gene regulation and the role of the antioxidant response element and the xenobiotic response element in transcriptional regulation is summarized. An overview of genetic polymorphisms in NQO1 is presented and biological significance for chemoprotection, cancer susceptibility and antitumor drug action is discussed.

Animals↗
PubMed2004

[Relationship between genetic polymorphism of tumor necrosis factor-alpha and susceptibility to intrauterine HBV infection].

OBJECTIVE: To study the possible relationship between tumor necrosis factor (TNF)-alpha-238G/A gene polymorphism and the susceptibility to intrauterine HBV infection. METHODS: Two hundred and fifty-six children, including 130 infants born to HBsAg positive mothers were divided into two groups: forty-five children with intrauterine HBV infection (group I) and 85 children without intrauterine HBV infection (group II), with a control group of 126. TNF-alpha-238G/A gene polymorphism was examined in all 256 children, by means of real-time quantitative fluorescent PCR. RESULTS: A significant difference of TNF-alpha-238A allele frequency was found between group I and group II (x2=6.797, P=0.009), and between group I and the controls group (x2=0.047, P=0.002), but there was no significant difference between group II and the control groups (x2=0.047, p=0.828). CONCLUSION: This study found that genetic polymorphism of tumor necrosis factor-a was associated with intrauterine HBV infection

Adult↗
PubMed1995

Identification of intra- and interspecific Leishmania genetic polymorphisms by arbitrary primed polymerase chain reactions and use of polymorphic DNA to identify differentially regulated genes.

Arbitrary primed polymerase chain reactions (AP-PCR) were used to amplify different polymorphic genomic DNA fragments from various Old World Leishmania species. Using four 10-mer AP primers, geographic isolates of L. donovani and various Old World species of Leishmania could be readily distinguished from one another by the pattern of amplified DNA products. Our studies confirmed two important characteristics of AP-PCR: its abilities to amplify a consistent pattern of DNA fragments from the genomes of different isolates of a single species and to identify genetic polymorphisms between the species isolates. We selected three polymorphic DNA fragments that differentiate L. donovani geographic isolates for further analysis. Sequence analysis of the clones derived from these three polymorphic fragments revealed eight unique sequences. Six of eight unique clones hybridized to distinct RNAs upon Northern-blot analysis. Three of these six clones hybridized to RNAs expressed differentially in in vitro grown L. donovani pro- and "amastigotes." One of the differentially expressed clones, LdE-6-1, exhibited restriction length polymorphisms that distinguished L. donovani from L. tropica and L. major. Comparative Northern blotting revealed that LdE-6-1 was differentially expressed in some members of the L. donovani species complex but not in L. major or L. tropica. These results demonstrate that AP-PCR can be used to generate products reflecting particular genes in organisms with low-complexity genomes.

Animals↗
PubMed2002

Genetic polymorphisms of glutathione S-transferase A1, the major glutathione S-transferase in human liver: consequences for enzyme expression and busulfan conjugation.

BACKGROUND: High-dose busulfan is widely used as part of conditioning regimens for patients who are undergoing hematopoietic stem cell or bone marrow transplantation. High plasma concentrations of busulfan have been linked to the occurrence of hepatic venoocclusive disease (VOD), a severe complication associated with a high mortality. Because conjugation with glutathione, the major route of biotransformation of busulfan, is predominantly catalyzed by the isozyme glutathione S-transferase A1 (GSTA1), we hypothesized that low expression or function of GSTA1 in liver caused by genetic polymorphisms may be the mechanism underlying VOD. METHODS: Immunoblot analysis of GSTA and measurement of busulfan-glutathione conjugation by liquid chromatography-mass spectrometry were performed in 48 normal human liver samples. To search for polymorphisms, the complete GSTA1 coding regions and the promoter fragment were sequenced. All results were compared by multivariate analysis. RESULTS: Absolute levels of GSTA protein and formation rates of busulfan-glutathione conjugate displayed a 7- and 8-fold range, from 240 to 1600 pmol/mg and 25 to 205 pmol/min per milligram of total cytosolic protein, respectively, and correlate (r2 = 0.49, P <.0001). A total of 8 single nucleotide polymorphisms (SNPs) of GSTA1 were identified, 1 of which was a silent mutation in exon 5 (A375G); all others were found in the promoter region. Haplotype analysis revealed the existence of 5 defined alleles. There was no significant relationship between any of the GSTA1 SNPs or haplotypes and either hepatic glutathione S-transferase A (GSTA) expression or GSTA1 function. CONCLUSIONS: The identified GSTA1 polymorphisms are not likely to be related to the VOD because they do not appear to be associated with changes in GSTA expression or function. Compared with other members of the GST family, GSTA1 displays surprisingly little variation.

Busulfan↗
PubMed2002

[Association between the genetic polymorphisms of beta2-adrenergic receptor gene and the asthma susceptibility and clinical phenotypes in a Chinese population].

OBJECTIVE: To determine whether genetic polymorphisms of beta2-adrenergic receptor gene affect asthma susceptibility and play a role in disease regulation. METHODS: One hundred and sixty-six unrelated childhood asthma cases and 32 families with 192 samples were studied. The polymorphisms at amino acid positions 16, 27, 164 and nucleic acid residue 523 were genotyped by polymerase chain reaction-restriction endonuclease digestion. RESULTS: The amino acid 164 Thr/Ile variant was seen only in the heterozygote form, and it occurred with a frequency of 3% which is similar to the published results among Caucasians. There were significant differences in the allele frequencies of the other 3 polymorphisms between Chinese and the published results among Caucasians (P<0.001). No polymorphism was found to be associated with total serum IgE, the number of positive prick skin test and FEV1. No significant association was noted between either the arginine-glycine 16 or the glutamine-glutamate 27 polymorphisms and the airway responsiveness to beta2-agonists in childhood asthma cases. CONCLUSION: In this study population, the authors were unable to confirm that the polymorphism of beta2-adrenergic receptor gene is a crucial factor of the susceptibility to asthma and a major genetic determinant of different clinical status.

Adult↗
PubMed2004

Association study of onset age, attempted suicide, aggressive behavior, and schizophrenia with a serotonin 1B receptor (A-161T) genetic polymorphism.

Located on the presynaptic and postsynaptic terminals of serotonergic neurons, serotonin 1B receptors (5-HT1B) are involved in the modulation of serotonergic activity. The implications of 5-HT1B study of animal models of schizophrenia and antipsychotic activity involving defective sensory processes suggest that this receptor may be involved in the pathogenesis of schizophrenic disorders. In a population-based association study, we tested the hypothesis that the allelic variant, A-161T, of the 5-HT1B gene confers susceptibility to schizophrenic disorders and is associated with age of onset, aggressive behavior and attempted suicide. We genotyped the A-161T polymorphism in 110 patients with schizophrenic disorders and in 215 normal controls. No association was demonstrated between 5-HT1B genotype or allele frequencies and schizophrenic disorders, except for a trend for later age at disease onset in A/A homozygote schizophrenics in comparison with A/T heterozygote patients (p = 0.071). No significant difference in genotype distribution was determined comparing patients with and without aggressive behavior, and those with and without a history of suicide attempt. These findings suggest that the investigated 5-HT1B genetic polymorphism does not play a major role in the pathogenesis of schizophrenic disorders.

Adult↗
PubMed1993

Double-strand DNA conformation polymorphisms as a source of highly polymorphic genetic markers.

The molecular basis for several apparent restriction fragment length polymorphisms of the porcine growth hormone gene was examined through DNA sequence analysis. Electrophoretic and sequence analysis suggest polymorphisms result from 1-3 base substitutions that affect double-strand DNA conformation and electrophoretic mobility. Two allelic forms of the porcine growth hormone 5' flank and four allelic forms of the second exon/intron region were identified. A marker system was developed which combined conformation polymorphisms with HaeII and DdeI RFLPs. Using this system, nine haplotypes were observed in samples from three US swine breeds. The data presented suggest that double-strand DNA conformation can be exploited in base substitution detection and development of highly polymorphic genetic marker systems.

Alleles↗
PubMed2001

Genetic polymorphism of the tumor necrosis factor (TNF)-alpha promoter region in families with localized early-onset periodontitis.

Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine that is able to induce tissue destruction and bone resorption. A G-to-A polymorphism at the -308 position of the TNF-alpha promoter region was suggested to influence TNF-alpha production. We had previously shown that monocytes of patients with localized early-onset periodontitis (EOP) secrete high levels of TNF-alpha compared to matched controls. The aim of the present study was to investigate the possible link between the -308 polymorphism in the TNF-alpha gene and EOP. Genomic DNA was extracted from the blood of 64 individuals from 11 nuclear families with EOP. The TNF-alpha polymorphism at -308 was assessed using allele-specific polymerase chain reaction. 77% of the tested adolescents were found to have the G/G genotype, and 23% had the A/G genotype. In the diseased subjects, 81% were with G/G genotype and 19% with A/G genotype. The healthy children had 74% G/G genotype, while 26% had A/G genotype. The differences between the disease group and the healthy group were not statistically significant. In summary, the present results could not demonstrate any link between EOP and genetic polymorphism in the -308 position of the TNF-alpha promoter.

Adenine↗