Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in most industrialized countries, accounting for one out of every two deaths in the United States. Disorders of the lipid transport system resulting from complex interactions among nutritional, environmental and genetic factors, play a very important role in the development of this disease. It has been proposed that low density lipoproteins (LDL) cause cholesterol deposition in the arterial wall, whereas high density lipoproteins (HDL) promote efflux of cholesterol from this site. Thus, low levels of HDL and/or high levels of LDL, have been associated with increased risk of CAD. Apolipoprotein A-I (Apo A-I) is the major protein component of HDL, and it has been proposed that the levels of this protein are a better predictor of risk of CAD than the level of cholesterol in HDL. The human Apo A-I gene has been characterized, and it has been found to be adjacent to the genes for apolipoproteins C-lll and A-lV on the long arm of chromosome 11. The cloning of these genes provides the appropriate tools to apply molecular genetic techniques to find differences between individuals at the gene level (restriction fragment length polymorphisms, RFLP) and to identify specific alleles at this particular gene locus which may be associated with a clinical phenotype, more specifically, premature CAD and familial hypoalphalipoproteinemia. In a preliminary study we have identified a Pst I restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary artery disease, lipid disorders and genetic polymorphisms. 289 7

We have recently reported that the human apolipoprotein A-I (apoA-I) and apolipoprotein C-III (apoC-III) genes are physically linked and that the presence of a DNA insertion in the apoA-I gene is correlated with apoA-I-apoC-III deficiency in patients with premature atherosclerosis. In addition, the presence of a polymorphic restriction endonuclease site (SacI) in the 3' noncoding region of apoC-III mRNA has been correlated with hypertriglyceridemia in humans. In this study, we report the isolation and characterization of cDNA clones containing the entire apoC-III mRNA coding sequence. The nucleotide-derived apoC-III amino acid sequence indicates that the apoC-III primary translational product contains a 20 amino acid N-terminal extension, which conforms with the general properties of known signal peptides, and is highly homologous to the recently reported rat apoC-III signal peptide. The DNA-derived apoC-III amino acid sequence differs from the previously reported apoC-III amino acid sequence at four amino acid residues. More specifically, at positions +32, +33, +37, +39, the DNA sequence predicts Glu, Ser, Gln, Ala, respectively, while the previously reported sequence specifies Ser, Gln, Ala, Gln, respectively. Finally, isolation and characterization of apoC-III cDNA clones, with or without the polymorphic SacI restriction site, indicated that the apoC-III nucleotide sequence corresponding to the Sac+ and Sac- clones differs at three nucleotide sites; however, the amino acid sequence specified by the Sac+ and Sac- alleles is identical.
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PMID:Isolation and characterization of cDNA clones corresponding to two different human apoC-III alleles. 298

A DNA sequence polymorphism, revealed by digestion of human DNA with the restriction endonuclease Sst-1 and hybridization with an apolipoprotein A-I complementary DNA clone, has been shown to be located in or close to the 3' noncoding region of the apolipoprotein C-III gene. This polymorphism is found in significantly increased prevalence (P less than 0.001) in Caucasian hypertriglyceridemic subjects compared with race-matched controls, and its distribution in normal individuals of differing racial origins is reported. Furthermore, no alteration of high density lipoprotein or apolipoprotein A-I and apolipoprotein C-III phenotypes was observed in individuals with or without the polymorphism.
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PMID:Deoxyribonucleic acid polymorphism in the apolipoprotein A-1-C-III gene cluster. Association with hypertriglyceridemia. 299 45

Decreased plasma high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I levels have been associated with premature coronary artery disease. We identified a PstI restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic. The absence and presence of this site, as determined by genomic blotting analysis of PstI-digested chromosomal DNA with the use of an apolipoprotein A-I gene probe, were associated with 3.3-kb and 2.2-kb hybridization bands, respectively. The 3.3-kb band appeared in 4.1 percent of 123 randomly selected control subjects and in 3.3 percent of 30 subjects with no angiographic evidence of coronary artery disease. In contrast, among 88 patients who had severe coronary disease before the age of 60, as documented by angiography, the 3.3-kb band occurred in 32 percent (P less than 0.0001). It was also found in 8 of 12 index cases (P less than 0.0001) of kindreds with familial hypoalphalipoproteinemia. In the two patient groups, the allele frequencies of the site that produced the 3.3-kb band were 17 and 42 percent, respectively, as compared with an allele frequency of only 2 percent in the control populations. Within kindreds with familial hypoalphalipoproteinemia and among first-degree relatives of patients with coronary artery disease, the 3.3-kb band was associated with decreased HDL cholesterol levels. Among all patients with coronary artery disease, 58 percent had HDL cholesterol levels below the 10th percentile of normal values; however, this frequency increased to 73 percent when patients with the 3.3-kb band were considered. These findings indicate that the polymorphism in the region between the apolipoprotein A-I and apolipoprotein C-III genes may be a useful marker for the risk of premature coronary artery disease and familial hypoalphalipoproteinemia.
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PMID:Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia. 308 5