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At least 775 records · Page 43Linked to original sources
PubMed1999

N-acetyltransferase 1 genetic polymorphism, cigarette smoking, well-done meat intake, and breast cancer risk.

N-Acetyltransferase 1 (NAT1), encoded by the polymorphic NAT1 gene, has been shown to be one of the major enzymes in human breast tissue that activates aromatic and heterocyclic amines. Humans are mainly exposed to these carcinogens through cigarette smoking and consumption of well-done meat. To test the hypothesis that variations in the NAT1 gene are related to breast cancer risk, particularly among women who smoke or consume high levels of well-done meat, a nested case-control study was conducted in a prospective cohort study of 41,837 postmenopausal Iowa women. Information on cigarette smoking and other breast cancer risk factors was obtained at the baseline survey conducted in 1986. DNA samples and information on the consumption of well-done meat were obtained, in the case-control study, from breast cancer cases diagnosed from 1992 to 1994 and a random sample of cancer-free cohort members. Genomic DNA samples obtained from 154 cases and 330 controls were assayed for 11 NAT1 alleles (NAT1*3, *4, *5, *10, *11, *14, *15, *16, *17, *19, and *22). The NAT1*4 allele was the predominant allele observed in this study population, accounting for 73.2% (72.4% in cases versus 73.8% in controls) of the total alleles analyzed. Compared to controls, breast cancer cases had a slightly higher frequency of the NAT1*10 allele (18.8% in cases versus 17.3% in controls) and a substantially higher frequency of the NAT1*11 allele (3.6% versus 1.2%). In multivariate analyses, we found a 30% [95% confidence interval (CI) = 0.8-1.9] elevated risk of breast cancer associated with the NAT1*10 allele and a nearly 4-fold (95% CI = 1.5-10.5) elevated risk associated with the NAT1*11 allele. The positive association of breast cancer with the NAT1*11 allele was more evident among smokers [odds ratio (OR) = 13.2, 95% CI = 1.5-116.0] and those who consumed a high level of red meat (OR = 6.1, 95% CI = 1.1-33.2) or consistently consumed their red meat well done (OR = 5.6, 95% CI = 0.5-62.7). The association of the NAT1*10 allele with breast cancer was mainly confined to former smokers (OR = 3.3, 95% CI = 1.2-9.5). These findings are consistent with a role for the NAT1 gene in the etiology of human breast cancer.

Aged↗
PubMed1999

[Genetic polymorphisms of the renin-angiotensin system and essential hypertension].

BACKGROUND: The renin-angiotensin system (RAS) plays an important role in blood pressure (BP) regulation. A number of RAS polymorphisms have been linked to essential hypertension (EH), but there is uncertainty about this association in other studies. We examined whether the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the M235T and T174M polymorphisms of the angiotensinogen (AGT) gene are associated with EH in a Spanish sample of hypertensive patients. MATERIAL AND METHODS: We studied 75 patients with EH (BP > 160/100 mmHg), aged 55 (8.5) years, 30 males, systolic BP (SBP) 182 +/- (22.1) mmHg, diastolic BP (DBP) 109 +/- (9.9) mmHg (mean [SD]) and a strong family history of the disease. As a control group, 75 healthy subjects with no family history of cardiovascular disease were studied. The polymorphisms were determined by PCR amplification of genomic DNA, followed by enzyme digestion for the AGT gene polymorphisms. RESULTS: The genotype distribution and the frequencies of the alleles of the three RAS polymorphisms were similar in hypertensive and control subjects. In addition, we did not find any compound effect of the I/D ACE gene and M235T AGT gene polymorphisms on BP levels in hypertensive and control subjects. CONCLUSIONS: In this sample, the contribution of the ACE I/D polymorphism and the AGT M235T and T174M polymorphisms in the development of EH seems to be less important than previously estimated.

Adult↗
PubMed1999

Genetic polymorphism of 5,10-MTHFR reductase gene in offspring of patients with myocardial infarction.

A family history of myocardial infarction is a major determinant of ischemic disease. A C->T677 polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified as a cause of mild hyperhomocysteinemia, a risk factor for arterial thrombosis. We have investigated the relationship between the MTHFR TT genotype and a family history of myocardial infarction in a cohort of 982 apparently healthy individuals. Subjects whose first-degree relatives suffered from a myocardial infarction, showed raised median age (p <0.001), total cholesterol (p <0.001) and plasma fibrinogen (p = 0.023) and a higher than normal frequency of C-reactive protein levels >0.33 mg/dl (p = 0.012). Moreover, when compared to subjects without such family history, a higher number of homozygotes for the T allele of the MTHFR gene (p = 0.027), and of the 4G allele of the plasminogen activator inhibitor-1 gene (p = 0.002) was found in the subsetting of the offspring of patients with myocardial infarction. In a multiple logistic regression analysis, age (OR 1.02 [95%-CI: 1.00-1.05]), total cholesterol (OR 1.40 [95%-CI: 1.14-1.71]), C-reactive protein levels >0.33 mg/l (OR: 1.87 [95%-CI: 1.10-3.20]), plasminogen activator inhibitor-1 4G/4G (OR: 1.84 [95%-CI: 1.27-2.66]), and MTHFR TT genotype (OR 1.62 [95%-CI: 1.08-2.42]), were all associated with a family history of myocardial infarction. Thus, the MTHFR TT genotype independently accounts for the risk of a family history for myocardial infarction in the present setting.

Adult↗
PubMed2000

Detection and genetic polymorphism of human herpes virus type 8 in endemic or epidemic Kaposi's sarcoma from West and Central Africa, and South America.

Kaposi's-sarcoma-associated herpesvirus(KSHV)/human-herpes-virus-8(HHV-8) sequences originally detected in AIDS-associated Kaposi's sarcoma have been found in almost every KS tested, whether endemic, classic, iatrogenic or epidemic. Most of the studies on African KS involved East African patients. We report herewith the study of 17 African or Guyanan KS patients, 3 with epidemic KS (EKS) from Central African Republic, 3 from Senegal (2 EKS and 1 endemic KS), 3 EKS from Cameroon and 8 from French Guiana (3 EKS and 5 endemic KS). Serum-specific antibodies directed against latent and/or lytic HHV-8 antigens were present in 16 of them (94%), detected either by immunofluorescence assay and/or by immunoperoxidase. Polymerase chain reaction (PCR), using specific primers for HHV-8 ORF26 (233 bp) and ORF75 (601 bp), was carried out on DNA extracted from KS cutaneous biopsies, clinically uninvolved skin biopsies and peripheral-blood mononuclear cells (PBMC). HHV-8 DNA was detected in 16 out of 16 (100%) KS biopsies, regardless of their origin or clinico-pathological sub-type, in 7 out of 15 (47%) normal skin samples and 7 out of 16 (44%) PBMC. Comparative PCR, carried out in 7 patients, regularly found a much higher viral load in KS biopsies than in autologous normal skin and PBMC samples. Sequencing of fragments of the ORF26 and of the ORF75 demonstrated that the 16 HHV-8 strains were of the A, B or C sub-type. Furthermore, sequences of the entire ORF K1 of 4 strains showed that these HHV-8 strains of African origin were of the A5 or the B sub-type.

AIDS-Related Opportunistic Infections↗
PubMed1998

A genetic polymorphism in the human HOXB1 homeobox gene implying a 9bp tandem repeat in the amino-terminal coding region. Mutations in brief no. 200. Online.

In man there are 39 homeobox genes of the HOX family in four loci, HOXA, HOXB, HOXC and HOXD on chromosomes 7, 17, 12, and 2. We discovered the existence of two major alleles, termed a and b, of gene HOXB1. They differ at a specific position in the 5' portion of the coding region. Sequencing the two alleles revealed that the allele HOXB1A, contains two copies of the 9bp sequence 5'ACAGCGCCC3', starting at position 65 of the coding region, whereas the allele HOXB1b contains three copies of this sequence (Fig. 1). As a consequence, the allele HOXB1b encodes a homeoprotein containing two copies of the tripeptide HisSerAla, starting at amino acid residue 25, which is present in only one copy in allele HOXB1a. We analyzed 250 individuals and found that the allelic frequencies of HOXB1a and HOXB1b were 78.8% and 21.2%. The murine homologue contains only one copy of the 9bp repeat (Fig. 1). 7 mouse strains, namely 129, BALB/c, C57BL/6, C57BL/10, CAST/Ei, C3H and SPRET/Ei, are homozygous for this allele. The allele present in gibbon and rhesus monkey appears to be identical to the human HOXB1b (Fig. 1).

Animals↗
PubMed2000

[Genetic polymorphism of 5 STR loci on chromosome 14 in Chinese Han].

OBJECTIVE: To understand the distribution of genes and genotypes of 5 STR loci on chromosome 14 in Chinese Han. METHODS: PCR and polyacrylamide gel electrophoresis were used to analyze the polymorphism of 5 STR loci (D14S742, D14S306, D14S606, D14S617, D14S611) on chromosome 14 in Chinese Han. RESULTS: 5 alleles and 13 genotypes, 5 alleles and 13 genotypes, 6 alleles and 13 genotypes, 9 alleles and 21 genotypes, and 6 alleles and 13 genotypes were observed at D14S742, D14S306, D14S606, D14S617 and D14S611, respectively. The frequencies of the most common allele at these five loci were 0.31, 0.31, 0.47, 0.35 and 0.29 respectively. CONCLUSION: These five loci are highly polymorphic in Chinese Han and their allele distribution is in good agreement with Hardy-Weinberg equilibrium.

China↗
PubMed2000

Association study between genetic polymorphisms in the 14-3-3 eta chain and dopamine D4 receptor genes and alcoholism.

BACKGROUND: The dopaminergic system may be involved in the development of alcoholism. As part of our ongoing studies on the association between alcoholism and dopaminergic genes, we report herein a mutation analysis of the 14-3-3 eta chain gene (YWHAH) and an association study between alcoholism and the YWHAH and dopamine D4 receptor gene (DRD4) polymorphisms. METHODS: Nucleotide mutations were investigated using single-strand conformation polymorphism methods. Associations were analyzed using a case-control design involving 185 Japanese alcoholics and 286 Japanese controls. RESULTS: Five polymorphisms, -147G>A, -134(GCCTGCA)2-4, IVS1+31(G)7-8, IVS1+73-74ins(G), and 753A>G, were detected on the YWHAH, and three of them were novel. No significant associations were found between alcoholism and these polymorphisms or two additional polymorphisms on DRD4 exon III and DRD4 -521C/T. CONCLUSIONS: YWHAH and DRD4 do not appear to play a major role in the development of alcoholism.

14-3-3 Proteins↗
PubMed2000

[Genetic polymorphism and asthma].

Several mutations have been found in genes encoding for proteins implied in the pathophysiology or the treatment of asthma. Until now, no causal role could not be highlighted. The mutations were mainly studied on gene coding for the beta 2 adrenergic receptor being able to be associated with modifications of the phenotype of asthma or even to modifications of response to some beta 2 agonists. Certain polymorphisms of the beta 2 adrenoceptor are associated with polymorphisms in genes coding for peptides controlling the expression of the beta 2 adrenoceptors. The interpretation of the effects observed must take into account this linkage disequilibrium.

Adrenergic beta-Agonists↗
PubMed2000

Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism.

Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9-9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0-13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.

Adenocarcinoma↗