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Results for “Genetic polymorphisms”

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At least 289 records · Page 16Linked to original sources
PubMed2001

Impact of genetic polymorphisms of 17-hydroxylase cytochrome P-450 (CYP17) and steroid 5alpha-reductase type II (SRD5A2) genes on prostate-cancer risk among the Japanese population.

Steroid hormones, especially testosterone, play important roles in the carcinogenesis of prostate cancer, and several studies have reported changes in risk with polymorphisms of genes involved in steroid metabolism. One example is the CYP17 gene, which has a polymorphic T-to-C substitution in the 5'-untranslated region giving rise to A1 (T) and A2 (C) alleles. Steroid 5alpha-reductase type II (SRD5A2), which converts testosterone to the metabolically more active dihydrotestosterone, exhibits 2 polymorphisms: V89L, which substitutes leucine for valine at codon 89, and A49T, which substitutes threonine for alanine at codon 49. We therefore designed a case-control study of 105 prostate-cancer patients and 210 controls with benign prostatic hyperplasia for the purpose of investigating the association between prostate-cancer risk and polymorphisms in the SRD5A2 and CYP17 genes among the Japanese. The frequency of the CYP17 A2/A2 genotype in cases (18.8%) was higher than in controls (14.5%). Compared with the A1/A1 genotype, the odds ratio for the A2/A2 genotype was 2.39 (95% confidence interval 1.04-5.46, p = 0.04). The frequency of the SRD5A2 LL genotype in cases (29.3%) was also slightly higher than in controls (24.6%), but this was not significant. Regarding the A49T polymorphism of SRD5A2, we could not detect the T allele in any of the examined samples. These data suggest a significant association between the CYP17 polymorphism and prostate-cancer risk among the Japanese.

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

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site, G1793A.

The importance of hyperhomocysteinemia, birth defects, and vascular diseases has been the subject of intense investigations. The polymorphic MTHFR mutations (C677T and A1298C) cause mild hyperhomocysteinemia, especially in homozygotes for C677T, but also in compound heterozygotes for C677T/A1298C. The subject of this report is the frequency of the polymorphic mutations in the MTHFR gene C677T, C1298A, and newly discovered mutation G1793A, as well as the association with MTRR polymorphic site A66G in different ethnic groups. Four ethnic groups were studied: African-Americans, Caucasians, Hispanics, and Ashkenazi Jews. There are statistically significant differences in the frequency of these alleles in the different populations studied, which impacts compound heterozygosity for such alleles in these populations. DNA samples obtained from the blood of healthy individuals of African-Americans, Hispanics, and Caucasians from south Texas were analyzed and compared to those obtained from Ashkenazi Jewish individuals. The polymorphic site, the G1793A allele, is least frequent among Ashkenazi individuals, 1.3%, compared to 6.9% among Caucasians (P = 0.001), 5.8% among Hispanics (P = 0.012), and 3.1% among African-Americans. The MTRR polymorphic site shows the lowest allele frequency among Hispanics, 28.6%, compared to 34% among African-Americans, 43.1% among Ashkenazi Jews (P = 0.002), and 54.4% among Caucasians (P < 0.0001). Statistically significant differences in allele frequencies of C677T and C1298A polymorphisms were also observed in these populations. Compound heterozygosity for multiple polymorphic alleles may play a role in birth defects and vascular diseases.

Alleles↗
PubMed2001

Abnormal folate metabolism and genetic polymorphism of the folate pathway in a child with Down syndrome and neural tube defect.

The association of neural tube defects (NTDs) with Down syndrome (trisomy 21) and altered folate metabolism in both mother and affected offspring provide a unique opportunity for insight into the etiologic role of folate deficiency in these congenital anomalies. We describe here the case of a male child with trisomy 21, cervical meningomyelocele, agenesis of corpus callosum, hydrocephaly, cerebellar herniation into the foramen magnum, and shallow posterior cranial fossa. Molecular analysis of the methylenetetrahydrofolate (MTHFR) gene revealed homozygosity for the mutant 677C-->T polymorphism in both the mother and child. The plasma homocysteine of the mother was highly elevated at 25.0 micromol/L and was associated with a low methionine level of 22.1 micromol/L. Her S-adenosylhomocysteine (SAH) level was three times that of reference normal women, resulting in a markedly reduced ratio of S-adenosylmethionine (SAM) to SAH and significant DNA hypomethylation in lymphocytes. The child had low plasma levels of both homocysteine and methionine and a reduced SAM/SAH ratio that was also associated with lymphocyte DNA hypomethylation. In addition, the child had a five-fold increase in cystathionine level relative to normal children, consistent with over-expression of the cystathionine beta synthase gene present on chromosome 21. We suggest that altered folate status plus homozygous mutation in the MTHFR gene in the mother could promote chromosomal instability and meiotic non-disjunction resulting in trisomy 21. Altered folate status and homozygous TT mutation in the MTHFR gene in both mother and child would be expected to increase the risk of neural tube defects. The presence of both trisomy 21 and postclosure NTD in the same child supports the need for an extended periconceptional period of maternal folate supplementation to achieve greater preventive effects for both NTD and trisomy 21.

Amino Acids, Sulfur↗
PubMed1980

Genetic polymorphisms in isolated Sherpa populations of Nepal.

Data are reported on the incidence of variants in the ABO blood group system, four red cell enzyme polymorphisms, and the PTU taster/non-taster polymorphism in 155 Sherpas and Tamangs living in two villages in the isolated Rolwaling valley in east Nepal. The incidence of phenotype AB was unexpectedly high in one village, as has been reported in some other high-altitude populations: possible causes are discussed. Each of the other polymorphisms has a different pattern of distribution between the populations studied; the Sherpas' allele distribution in the phosphoglucomutase (PGM) system seems to be distinct from the surrounding populations'. ABO gene frequencies suggest affinities between Sherpas in the study villages and old- and new-clan Sherpa populations, respectively, in Solu and Khumbu.

ABO Blood-Group System↗
PubMed1983

Genetic polymorphism of lambda 1 and lambda 3 immunoglobulin light chains in the Mus subgenus.

Several inbred or partially inbred mouse strains derived from wild mice of different Mus subgroups were surveyed for expression of lambda 1 light chain. One strain, SPE, expressed little or no lambda 1 chains. Two populations of antibodies were obtained by immunization of SPE mice with lambda 1 light chain isolated from the BALB/c J558 (alpha, lambda 1) myeloma protein. One population of antibodies recognized lambda 1 allotypic determinants located on the C terminal fragment beginning at the residue 176. A second population was directed against epitopes present on both lambda 1 and lambda 3 chains. These determinants, which were detected in all strains tested with the exception of SPE, were located in the V region. This result is in concordance with recent DNA studies showing that the lambda 1 and lambda 3 isotype use the same V lambda 1 genes (Blomberg, B. et al., Proc. Natl. Acad. Sci. USA 1981. 78: 3765). Whether the V epitopes recognized by SPE antibodies are allotypic or isotypic in nature is not certain.

Animals↗
PubMed1989

Antibody 12-15 cross-reacts with mouse Fc gamma receptors and CD2: study of thymus expression, genetic polymorphism and biosynthesis of the CD2 protein.

Previously we described a monoclonal antibody (mAb 12-15) that reacted with murine Fc receptor proteins (beta 1, beta 2 and alpha) and an undefined molecule of 37 kDa (beta 3) on certain types of cells. Here we present serological and biochemical evidence that the beta 3 chain is expressed on mouse thymocytes and that it is identical to the CD2 antigen. By immunofluorescence staining and cytofluorographic analysis greater than 95% of thymocytes were positive. Brightly staining cells coincided with cortisone-resistant thymocytes suggesting that mature thymocytes expressed higher levels of the antigen. Biosynthetic labeling of DBA/2 thymocytes with [35S]methionine showed that the size of the CD2 precursor molecule was 43 kDa which was processed to approximately 55-65 kDa in the mature molecule. mAb 12-15 was also reactive with the tunicamycin-treated form of the CD2 antigen suggesting that the cross-reactive epitope was of protein nature. Comparison of different mouse strains indicated that two molecular forms of CD2 exist. On BALB/c thymocytes, the relative mass of the native molecule was approximately 60-70 kDa (CD2.1) and slightly larger than in DBA/2 (CD2.2). Following endoglycosidase F treatment both proteins still showed a slight difference in electrophoretic mobility. Several inbred mouse strains were analyzed for expression of CD2 forms. When mAb 12-15 was used in cytotoxic T lymphocyte inhibition experiments using specific CTL and tumor target cells it was found that the antibody could specifically inhibit CTL-mediated lysis presumably by interfering with CD2 function.

Animals↗
PubMed1997

Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

HIV Infections↗
PubMed1991

Genetic polymorphisms of the A and B subunits of human coagulation factor XIII in mainland Italy and Sardinia: description of a new FXIIIA variant allele.

The distribution of the two alleles of FXIIIA and the three alleles of FXIIIB were studied in populations from mainland Italy and from Sardinia. The frequencies of the FXIIIA*2 allele were 0.266 and 0.265. The frequencies of FXIIIB*1 were 0.787 and 0.765; of B*2, 0.070 and 0.094; of B*3, 0.143 and 0.141. A new cathodal FXIIIA allele (A*7) was described in the Rome sample. No significant difference in the distribution of allele frequencies for either system was found between the two populations studied. For typing both markers, good results were also obtained by using whole blood instead of plasma.

Alleles↗
PubMed1992

Genetic polymorphism of apolipoprotein H (beta 2-glycoprotein I) in African blacks from the Ivory Coast.

The apolipoprotein H (APO H) polymorphism was analyzed in the Negroid population from the Ivory Coast using polyacrylamide gel isoelectric focusing, followed by immunoblotting. The gene frequencies of alleles APO H*1, APO H*2, APO H*3 and APO H*4 were calculated to be 0.012, 0.921, 0.047, and 0.020, respectively. The assumption that APO H*4 represents a Negroid marker allele is supported by this population study.

Alleles↗
PubMed1997

Characterization of stereoselectivity and genetic polymorphism of the debrisoquine hydroxylation in man via analysis of urinary debrisoquine and 4-hydroxydebrisoquine by capillary electrophoresis.

Using capillary zone electrophoresis with a phosphate buffer at pH 2.5 containing 50 mM heptakis-(2,3,6-tri-O-methyl)-beta-CD as chiral selector, the separation of the enantiomers of the main metabolite of debrisoquine (DEB), 4-hydroxydebrisoquine (4-OHDEB), is reported. For extraction of underivatized urinary DEB, S-4-OHDEB and R-4-OHDEB, a procedure using disposable cartridges containing a polystyrene-based polymer was developed. A few nL of the extracts were analyzed in a 60 cm fused-silica capillary of 50 microns ID and solute detection was effected at 195 nm. For all three compounds, a mean (n = 5) recovery of about 73% and a detection limit of about 150 ng/mL were noted. Data obtained with urines that were received for routine phenotyping with DEB and mephenytoin confirmed the almost exclusive formation of S-4-OHDEB. Under the described conditions, no R-4-OHDEB could be detected. With these data and those obtained employing no chiral selector in the buffer, differentiation between extensive metabolizer phenotypes (EM) and poor metabolizer phenotypes (PM) for DEB was unambiguously possible by the presence of a significant peak and no (or minor) peak for 4-OHDEB, respectively. Data obtained for ten EM subjects and five PM subjects were found to agree with those generated by the routine assay based on gas chromatography. The capillary electrophoretic assays described are simple, reproducible (relative standard deviation of peak area ratios < 3%), require no sample derivatization, consume no halogenated organic solvents, and operate with inexpensive separation columns as well as small amounts of chemicals.

Debrisoquin↗
PubMed2003

Genetic polymorphism of drug-metabolizing enzymes and styrene-induced DNA damage.

A cross-sectional study was carried out on 48 workers exposed to styrene and 14 unexposed healthy controls in order to investigate the genotoxic potential of styrene exposure. DNA damage was assessed in peripheral blood leukocytes (WBCs) by the comet assay. Polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and the gene encoding microsomal epoxide hydrolase (EPHX) were characterized to assess their possible modifying role in styrene metabolism and subsequent DNA damage. Exposed workers showed significantly higher levels of DNA damage compared to controls. Among workers, the GSTM1 and GSTT1 polymorphisms significantly affected comet parameters. Subjects bearing a GSTM1pos genotype showed a significantly higher proportion of damaged nuclei compared to people lacking GSTM1-1 expression (GSTM1null), whereas GSTT1pos workers showed significantly lower DNA damage than GSTT1null individuals. Styrene-7,8-oxide (SO)-induced DNA damage was assessed in vitro in WBCs isolated from the healthy controls. A clear dose-response relationship at micromolar doses of SO was found for the whole group. WBCs collected from subjects bearing the homozygous wildtype GSTP1 genotype showed a significant protection compared to cells from subjects bearing at least one GSTP1 variant allele. The field survey confirms that styrene exposure is associated with increased DNA damage and indicates a modulating role for GSTM1 and GSTT1 genotypes. In vitro experiments suggest that the extent of SO-induced DNA strand breaks depends, at least in part, on interindividual differences in GSH-conjugation capabilities.

Adult↗