PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Molecular polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed2002

Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine.

Human CYP3A enzymes play a pivotal role in the metabolism of many drugs, and the variability of their expression among individuals may have a strong impact on the efficacy of drug treatment. However, the individual contributions of the four CYP3A genes to total CYP3A activity remain unclear. To elucidate the role of CYP3A7, we have studied its expression in human liver and intestine. In both organs, expression of CYP3A7 mRNA was polymorphic. The recently identified CYP3A7*1C allele was a consistent marker of increased CYP3A7 expression both in liver and intestine, whereas the CYP3A7*1B allele was associated with increased CYP3A7 expression only in liver. Because of the replacement of part of the CYP3A7 promoter by the corresponding region of CYP3A4, the CYP3A7*1C allele contains the proximal ER6 motif of CYP3A4. The pregnane X and constitutively activated receptors were shown to bind with higher affinity to CYP3A4-ER6 than to CYP3A7-ER6 motifs and transactivated only promoter constructs containing CYP3A4-ER6. Furthermore, we identified mutations in CYP3A7*1C in addition to the ER6 motif that were necessary only for activation by the constitutively activated receptor. We conclude that the presence of the ER6 motif of CYP3A4 mediates the high expression of CYP3A7 in subjects carrying CYP3A7*1C.

Adult↗
PubMed1986

Molecular localization and polymorphism of HLA class II restriction determinants defined by Mycobacterium leprae-reactive helper T cell clones from leprosy patients.

MHC class II molecules carry the restriction determinants (RDs) for antigen presentation to antigen-specific Th lymphocytes. This restriction of T cell activation endows those molecules with a key role in the induction and regulation of antigen-specific immune responses. Moreover, class II molecules are the products of class II immune response (Ir) genes. The polymorphism of these Ir genes leads to genetically controlled differences in immuneresponsiveness between different individuals. An important human example is leprosy, in which HLA class II-linked Ir genes determine the immune response against Mycobacterium leprae, the causative organism of the disease. Since the immune response against M. leprae is entirely dependent on Th cells, the HLA class II-linked Ir gene products may well regulate the immune response by controlling the presentation of M. leprae antigens to Th cells. We therefore have investigated the HLA class II RD repertoire of M. leprae-reactive Th cell clones (TLC) by means of extensive panel and inhibition studies with fully class II-typed allogeneic APCs and well-defined HLA class II-specific mAbs. The TLC studied (n, 36) proliferated specifically towards M. leprae, produced IFN-gamma upon activation, and had the CD3+CD4+CD8- phenotype. The results show in the first place that the majority of the RDs for M. leprae reside on DR and not on DP or DQ molecules. This indicates a major role for DR molecules in the immune response to M. leprae and suggests that these molecules are the main products of M. leprae-specific Ir genes. Furthermore, since the expression of DR molecules is much stronger than that of DP and DQ molecules, these findings suggest that the localization of RDs for M. leprae on class II molecules correlates with the quantitative expression of these molecules. The observation that the RDs on DR molecules coded by a DR4 haplotype were situated only on those DR molecules that are known to be highest in expression can be explained in the same way. Second, four distinct RDs related with but not identical to the Dw13 allodeterminant were carried by the DR+DRw53- (alpha beta 1) molecules of a DR4Dw13 haplotype. Since the known amino acid residue differences between the allelic DR4 related Dw beta 1 chains cannot explain the observed RD-polymorphism, this observation suggests that multiple distinct RDs unique for the DR4Dw13 haplotype are expressed by these molecules. Only 2 of 36 TLC were not restricted by DR.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1992

[Molecular pharmacology of polymorphic arylamine N-acetyltransferase involved in the metabolism of arylamine drugs].

Polymorphic arylamine N-acetyltransferase in the liver determines the N-acetylation rate of arylamines, which has been implicated in the effects and toxicity of amine- and hydrazine-containing drugs. Recently we have demonstrated that there are four types of gene for polymorphic N-acetyltransferase and that gene 1 gives rise to high N-acetyltransferase activity, while gene 2, 3, and 4 correspond to low N-acetyltransferase activity. Analysis of four genes revealed that the point mutations in genes 2, 3, and 4 result in a loss of a restriction site: a BamHI site for gene 2, a TaqI site for gene 3, and a KpnI site for gene 4. Therefore all four genes can be discriminated by genomic Southern blot analysis and also by PCR amplification of the respective site followed by digestion with an appropriate endonuclease.

Acetylation↗
PubMedDate not supplied

[Acid-stable proteinase inhibitor from the urine of pregnant women, the properties of the highly purified preparation and the isolation of a monospecific antiserum].

Two highly purified forms of acid-stable proteinase inhibitor from urine of pregnant women with nephropathies (Mr 22000 and 32000, ASI-22 and ASI-32, respectively) were obtained. The preparations were homogenous in molecular mass and polymorphous in molecular charge (pI from 3.9 to 4.2). ASI-22 an ASI-32 effectively inhibited trypsin and chymotrypsin (Ki approximately 1 x 10(-8)-1 x 10(-9) M, ka approximately 10(5)M-1 sec-1, kd approximately 3 x 10(-4) sec-1) by the permanent mechanism of action. Both forms inhibited the esterase activity of pancreatic pig elastase by the progressive mechanism of action (ki approximately 1 x 10(4)M-1 min-1 at 37 degrees). Rabbit monospecific antiserum to total ASI-22 and ASI-32 preparation was obtained 1 ml of the anti-ASI-serum contained 95 micrograms of antibodies. Total ASI preparations was immunochemically homogenous and had antigenic similarity to inter-alpha-trypsin inhibitor from human plasma.

Animals↗
PubMed1995

[The molecular mechanism of polymorphism of S-mephenytoin hydroxylative metabolism].

The hydroxylation of S-mephenytoin exhibits a genetic polymorphism in humans and there are a large interethnic differences in the frequency of the poor metabolizer phenotype. A S-mephenytoin P450-hydroxylase termed P450 UK was purified and identified to be CYP 2C19 by amino-terminal amino acid analyses. The levels of P450 2C19 and the ability of the human liver samples to 4'-hydroxylate S-mephenytoin were found to be strongly correlative. Recent report showed that the principle defect in S-mephenytoin poor metabolizers is a single base pair (G-->A) mutation in exon 5 of CYP 2C19 resulting in an aberrantly spliced mRNA and a non-functional P450 2C19 protein in liver of S-mephenytoin PM. Further investigations demonstrate that this major defect is responsible for about 75% of poor metabolizer phenotype in both caucasians and orientals who are homozygous for S-mephenytoin hydroxylation defect. This genetic defect (CYP 2C19) also affects metabolism of several other widely clinical used drugs.

Aryl Hydrocarbon Hydroxylases↗
PubMed2004

Impact of molecular speciation on crystal nucleation in polymorphic systems: the conundrum of gamma glycine and molecular 'self poisoning'.

The polymorphism of the simple amino acid glycine has been known for almost a century. It is also known that in aqueous solutions, at the isoelectric point (pI 5.9), the metastable alpha polymorph crystallizes, while the stable gamma form of glycine only nucleates at high and low pH. Despite the importance of understanding the process by which crystals nucleate, the solution and solid-state chemistry underlying this simple observation have never been explored. In this contribution, we have combined solution chemistry, crystallization, and crystallographic data to investigate the mechanisms by which this effect occurs. It is concluded that solution speciation and the consequent interactions between charged species and developing crystal nuclei determine the structural outcome of the crystallization process.

Crystallization↗
PubMed1993

Comparison of PCR fingerprinting, by random amplification of polymorphic DNA, with other molecular typing methods for Candida albicans.

Fingerprinting by random amplification of polymorphic DNA (RAPD) was compared with existing molecular typing systems for Candida albicans. Fifteen isolates were chosen, including three from the same patient; these gave 14 distinct karyotypes by pulsed-field gel electrophoresis (PFGE) and 7 different DNA types by EcoRI-generated restriction fragment length polymorphisms (RFLPs). RAPD with primer I (5'GCTGGTGG3') gave 5 types, whereas primer II (5'GCGCACGG3') yielded 11 types. Combining the results from both primers, all isolates were unique by RAPD with the exception of the three from the same patient. RAPD provided a fast, economical and reproducible means of typing C. albicans with a level of discrimination approaching that of PFGE.

Base Sequence↗
PubMed2001

[Molecular-genetic analysis of polymorphism of the DXS532 locus in people from the Volga-Ural region].

The DXS52 polymorphic locus mapping to the 5'-region of the blood-clotting factor VIII gene on the X chromosome was genotyped in seven Volga-Ural ethnic groups (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). A total of 47 different genotypes and 15 allelic variants of this locus were described. Substantial intra- and interpopulation heterogeneity of the ethnic groups studied in respect to frequency and distribution of the DXS52 alleles and genotypes was demonstrated. The unimodal DXS52 allele frequency distribution pattern with the peak at 1690 bp was typical to Mordovians and Komis. Chuvashes and Maris, as well as Udmurts, were characterized by bimodal frequency distribution patterns, with the peaks at 1690 and 670 bp, and 1690 and 1390 bp, respectively. Moreover, Bashkirs and Tatars displayed trimodal DXS52 allele frequency distribution patterns with the peaks at 1690, 1390, and 670 bp. The DXS52 allele frequency distribution patterns described in populations of the Volga-Ural region were found to be remarkably different from those established for the mixed Moscow population and the population of Western Europe. These data indicate that the DXS52 locus is highly informative, and this polymorphic system can serve as a molecular marker for population genetic studies.

Chromosome Mapping↗
PubMedDate not supplied

[Genetic engineering of peptide hormones. II. Possible polymorphism of bovine preprolactin. Molecular cloning data].

The primary structure of an insert from a clone isolated from the bovine pituitary cDNA library by hybridization with prolactin-specific probe has been determined. It was found that the rearrangement of cDNA took place in the process of cloning. The rearrangement includes the inversion of 5'-terminal and the deletion of the central part of cDNA. However from the structure of the insert we were able to deduce the sequences of 5'- and 3'-terminal regions of bovine preprolactin mRNA (257 and 551 bases long). The comparison of these sequences with those published earlier revealed several differences in the primary structure. The most essential of them is the additional triplet coding for alanine in position of -22 of the signal peptide. The heterogeneity of bovine preprolactin mRNA in the region coding for the signal peptide is considered to be a consequence of alternative splicing as it was shown for rat preprolactin mRNA.

Amino Acid Sequence↗
PubMed2001

Optimization of random amplification of polymorphic DNA analysis for molecular subtyping of Escherichia coli O157.

Random amplification of polymorphic DNA (RAPD) analysis using the polymerase chain reaction has proved to be a useful technique in the epidemiological investigation of micro-organisms but may suffer from a lack of reproducibility in poorly optimized protocols. In this study a method of obtaining reproducible genomic fingerprints using RAPD analysis of Escherichia coli O157 is described. By systematic optimization of reaction conditions and selection of suitable primers, reproducible and discriminatory profiles could be obtained from all E. coli O157 strains tested. In addition, two other methods of obtaining reproducible profiles from E. coli O157 strains without the need to purify genomic DNA are described.

Buffers↗
PubMed2000

Molecular epidemiology of genetic polymorphisms in estrogen metabolizing enzymes in human breast cancer.

Epidemiologic studies indicate that most risk factors for breast cancer are related to reproductive and hormonal factors. For a number of years, the mechanism for estrogens in carcinogenesis was thought to be that of mitotic stimulation, with the growth promotion of ductal epithelial cells harboring precursor mutations in the breast. However, evidence is now available that estrogens may act as initiators of cellular alterations and tumorigenesis. Investigation and measurement of serum levels of estrogens in epidemiologic studies may, therefore, be misleading, because they may reflect levels quite different from those of hormone metabolites to which the target tissue is exposed. Proportions of hormone metabolites may be estimated by evaluation of associations between breast cancer risk and genetic polymorphisms in enzymes involved in hormone metabolism. A number of molecular epidemiologic studies have been conducted to evaluate associations between polymorphic genes involved in steroid hormone metabolism (i.e., CYP17, COMT, CYP1A1, CYP19, GST, and MnSOD) that may account for a proportion of enzymatic variability, and results are discussed in this review. There are strengths and limitations to such an approach, foremost of which may be the lack of insight into the extent to which individual variability in estrogen exposure may be explained by allelic variation. Variability in other endogenous and exogenous factors that impact parent hormones and their metabolites along activation and conjugation pathways may also affect associations in case-control comparisons. This and other possible reasons for inconsistencies in results of molecular epidemiologic studies are discussed. Contributions from population-based studies and those from the laboratory may together move this field ahead and more clearly elucidate the basis of hormonally related cancers, identifying etiologic factors and susceptible populations for preventive strategies.

Breast Neoplasms↗
PubMed1990

Molecular basis for a polymorphism of human Fc gamma receptor II (CD32).

The IgG Fc receptor II on human monocytes is polymorphic in its ability to bind mIgG1, and its isoelectric focusing pattern. To study the molecular basis of this polymorphism, a cDNA library from cell line K562, expressing two different allelic forms (high responder [HR] and low responder [LR]) of Fc gamma RII, was used for cDNA cloning. We report the isolation and identification of different Fc gamma RII cDNA clones, comprising the LR form of Fc gamma RII, as was evident from studies using a new HR-specific anti-Fc gamma RII mAb 41H16, and from rosetting experiments. Sequence analysis revealed that HR and LR forms differ by two amino acids, both located in the external domain. In the cloned LR form, a glutamine is substituted by a tryptophan residue at aa position 27, located in the first Ig-like domain, and an arginine residue by a histidine residue at aa position 131 in the second Ig-like domain. Furthermore, an Fc gamma RII cDNA clone was isolated with a deletion of 123 bp, overlapping the predicted transmembrane segment. Data showing the presence of an alternatively spliced mRNA detected by using polymerase chain reaction (PCR) might suggest the existence of a soluble form of the human Fc gamma RII, in addition to the membrane-bound forms.

Alleles↗
PubMed2000

[Molecular genetic analysis of polymorphism of the HindII and (CA)-repeat of the factor VIII gene loci in people of the Volgo-Ural region].

Molecular genetic analysis of polymorphism of the factor VIII gene at loci HindIII (intron 19) and (CA)-repeats (intron 13) was performed in seven ethnic groups of the Volga-Ural region (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). The allelic frequency of the HindIII locus was shown to be similar in these ethnic groups. The ethnic groups were more heterogeneous with regard to the genotype and allele frequencies of (CA)-repeats, which indicates that this polymorphic system can be used to characterize the genetic structure of the Volga-Ural human populations.

Alleles↗