Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic lipase (HL) activity may influence susceptibility to coronary artery disease (CAD). Association between the single nucleotide polymorphisms (SNPs) in the HL gene with the occurrence of CAD has been investigated thoroughly, but to date most studies focused on the base variation in the promoter of HL gene, little is known about the variation in the coding region. In present study, the SNP in all exons of the HL gene were analyzed. All 9 exons with their flanking sequences of the HL gene were amplified from the Chinese patients with CAD and normal controls by PCR technique, and the PCR products were detected by denaturing high performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. As the result, a novel SNP A(+884)-->G within the sixth exon of HL gene was found, the 276 codon AAA was changed into AGA and resulted in the substitution of arginine for lysine. Compared with the control group, more CAD patients carried the G+884 allele (AG+GG) (54.9% vs. 41.5%, chi(2)=6.164, df=2, P=0.046). The prevalence of the G+884 allele was significantly higher in the CAD patients than that in control subjects (31.4% vs. 21.3%, chi(2) =4.652, df=1, P=0.031). Data from the linkage disequilibrium analysis showed that the A(+884)-->G polymorphism was strong in linkage disequilibrium with the T(-2)-->C variation we identified previously(D'=0.699, 0.742 in CAD patients and controls, respectively), and the frequency of the C(-2)/G(+884) haplotype (mutation) is significantly higher in CAD patients than that in controls (0.253 vs. 0.172, P<0.05).
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PMID:A novel polymorphism A(+884)-->G in the hepatic lipase gene and its association with coronary artery disease. 1288 29

To analyse the mechanism by which rare codons near the initiation codon inhibit cell growth and protein synthesis, we used the bacteriophage lambda int gene or early codon substitution derivatives. The lambda int gene has a high frequency of rare ATA, AGA and AGG codons; two of them (AGA AGG) located at positions 3 and 4 of the int open reading frame (ORF). Escherichia coli pth (rap) cells, which are defective in peptidyl-tRNA hydrolase (Pth) activity, are more susceptible to the inhibitory effects of int expression as compared with wild-type cells. Cell growth and Int protein synthesis were enhanced by overexpression of Pth and tRNAArg4 cognate to AGG and AGA but not of tRNAIle2a specific for ATA. The increase of Int protein synthesis also takes place when the rare arginine codons AGA and AGG at positions 3 and 4 are changed to common arginine CGT or lysine AAA codons but not to rare isoleucine ATA codons. In addition, overexpression of int in Pth defective cells provokes accumulation of peptidyl-tRNAArg4 in the soluble fraction. Therefore, cell growth and Int synthesis inhibition may be due to ribosome stalling and premature release of peptidyl-tRNAArg4 from the ribosome at the rare arginine codons of the first tandem, which leads to cell starvation for the specific tRNA.
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PMID:The pair of arginine codons AGA AGG close to the initiation codon of the lambda int gene inhibits cell growth and protein synthesis by accumulating peptidyl-tRNAArg4. 1289 27

In humans, eight types of histone H1 exist (H1.1-H1.5, H1 degrees , H1t and H1oo), all consisting of a highly conserved globular domain and less conserved N- and C-terminal tails. Although the precise functions of these isoforms are not yet understood, and H1 subtypes have been found to be dispensable for mammalian development, it is now clear that specific functions may be assigned to certain individual H1 subtypes. Moreover, microsequence variations within the isoforms, such as polymorphisms or mutations, may have biological significance because of the high degree of sequence conservation of these proteins. This study used a hydrophilic interaction liquid chromatographic method to detect sequence variants within the subtypes. Two deviations from wild-type H1 sequences were found. In K562 erythroleukemic cells, alanine at position 17 in H1.2 was replaced by valine, and, in Raji B lymphoblastoid cells, lysine at position 173 in H1.4 was replaced by arginine. We confirmed these findings by DNA sequencing of the corresponding gene segments. In K562 cells, a homozygous GCC-->GTC shift was found at codon 18, giving rise to H1.2 Ala17Val because the initial methionine is removed in H1 histones. Raji cells showed a heterozygous AAA-->AGA codon change at position 174 in H1.4, corresponding to the Lys173Arg substitution. The allele frequency of these sequence variants in a normal Swedish population was found to be 6.8% for the H1.2 GCC-->GTC shift, indicating that this is a relatively frequent polymorphism. The AAA-->AGA codon change in H1.4 was detected only in Raji cells and was not present in a normal population or in six other cell lines derived from individuals suffering from Burkitt's lymphoma. The significance of these sequence variants is unclear, but increasing evidence indicates that minor sequence variations in linker histones may change their binding characteristics, influence chromatin remodeling, and specifically affect important cellular functions.
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PMID:Characterization of sequence variations in human histone H1.2 and H1.4 subtypes. 1600 66

In order to survive prolonged treatment with antiretroviral nucleoside analogs, the human immunodeficiency virus type 1 (HIV-1) is selectively forced to acquire mutations in the reverse transcriptase (RT) gene. Some of these mutations are more common than others and have become markers for antiretroviral resistance. For the early detection of these markers, a novel MultiCode-RTx one-step testing system to rapidly and simultaneously characterize mixtures of HIV-1 targets was designed. For cDNA, nucleotide polymorphisms for codon M184V (ATG to GTG) and K65R (AAA to AGA) could be differentiated and quantified even when the population mixture varied as much as 1 to 10,000. Standard mixed-population curves using 1 to 100% of the mutant or wild type generated over 4 logs of total viral particle input did not affect the overall curves, making the method robust. The system was also applied to a small set of samples extracted from infected individuals on nucleoside reverse transcriptase inhibitor therapy. Of 13 samples tested, all were positive for HIV and 10 of the 13 genotypes determined were concordant with the line probe assay. MultiCode-RTx could be applied to other drug-selected mutations in the viral genome or for applications where single-base changes in DNA or RNA occur at frequencies reaching 0.01% to 1%, respectively.
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PMID:Quantifying mixed populations of drug-resistant human immunodeficiency virus type 1. 1604 44

Non-optimal (rare) codons have been suggested to reduce translation rate and facilitate secretion in Escherichia coli. In this study, the complete genome analysis of non-optimal codon usage in secretory signal sequences and non-secretory sequences of Streptomyces coelicolor was performed. The result showed that there was a higher proportion of non-optimal codons in secretory signal sequences than in non-secretory sequences. The increased tendency was more obvious when tested with the experimental data of secretory proteins from proteomics analysis. Some non-optimal codons for Arg (AGA, CGU and CGA), Ile (AUA) and Lys (AAA) were significantly over presented in the secretary signal sequences. It may reveal that a balanced non-optimal codon usage was necessary for protein secretion and expression in Streptomyces.
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PMID:Whole genome analysis of non-optimal codon usage in secretory signal sequences of Streptomyces coelicolor. 1664 95

In an effort to improve the knowledge about the rules which direct the effect of the early ORF sequences on translation efficiency, we have analyzed the effect of pairs of the six arginine codons at the second and third positions on the expression of lacZ variants. Whereas the pairs of identical AGA or AGG codons were favorable for the gene expression, identical pairs of each of the four CGN codons were very inefficient. This result was unexpected because tandems of AGA or AGG codons located in more internal gene positions provoke deficient expression whilst internally located CGU and CGC are the most abundant and efficiently translated arginine codons. The mixed combinations of AGA and each of the CGN codons usually resulted in efficient rates of lacZ expression independently of the peptidyl-tRNA propensity to dissociate from the ribosome. Thus, the variant harboring the pair of AGA codons was expressed as efficiently as the variant carrying a pair of AAA codons in the same positions, a configuration reported as one of the most common and efficient for gene expression. We explain these results assuming that the presence of adenines in these early positions enhance gene expression. As expected, specific mRNA levels correlated with the intensity of lacZ expression for each variant. However, the induction of lacZ AGA AGA gene in pth cells accumulated peptidyl-tRNA(Arg4) as well as a short 5'-proximal lacZ mRNA fragment suggesting ribosome stalling due to depletion of aminoacylated-tRNA(Arg4).
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PMID:Efficient expression of gene variants that harbour AGA codons next to the initiation codon. 1772 48

Accumulating evidence indicates that activation of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) dampens the inflammation cascade and inhibits tumor growth of the lung, suggesting that it has tumor suppressor functions. We performed a case-control study of 500 incident lung cancer cases and 517 age- and sex frequency-matched cancer-free controls in a Chinese population to investigate the role of 11 selected single nucleotide polymorphisms (SNPs) of PPAR-gamma in the etiology of lung cancer. We found that decreased lung cancer risk was statistically significantly associated with seven SNPs (P = 0.0004 for rs13073869 and 0.0130 for rs1899951 in a dominant model; P = 0.0310 for rs4135247 in a log-additive model; and P = 0.0468 for rs2972162, 0.0175 for rs709151, 0.0172 for rs11715541 and 0.0386 for rs1175543 in an overdominant model). Consistent with these results of single-locus analysis, both the haplotype and the diplotype analyses revealed a protective effect of the haplotype 'AGA' and 'AAA' of rs13073869, rs1899951 and rs4135247. Furthermore, we observed a statistically significant interaction between the rs1899951 and cigarette smoking. Our results indicate that PPAR-gamma polymorphisms and their interaction with smoking may contribute to the etiology of lung cancer. These findings need to be validated in larger, preferably population-based, studies including different ethnic groups.
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PMID:Genetic variants in peroxisome proliferator-activated receptor-gamma gene are associated with risk of lung cancer in a Chinese population. 1818 57

Human Relaxin 2 is an insulin-related peptide hormone with a mass of 19,084 Da. The mRNA contains a number of arginine codons that are rarely used by Escherichia coli to produce highly expressed proteins. As a result, expressing this recombinant protein in E. coli is problematic. When human Relaxin 2 was expressed in E. coli BL21 (DE3), several forms of the protein were made. One species had the expected molecular weight (19,084 Da). A second species observed had a molecular weight of 21,244 Da. A third minor species had a molecular weight of 17,118 Da. These aberrant molecular weights can be explained as follows. First, a sequence CGA-AAA-AAG-AGA, containing the rare arginine codons CGA and AGA was the site of the +1 frameshift that generated the 21,244 Da species. Since there was a limited supply of this arginyl-tRNA, the peptidyl-tRNA moved +1 nucleotide to occupy the codon and resumed protein synthesis. Second, a -1 frameshift associated with 'slippery A' sequence XXA-AAA-AAG accounted for 10% of the product with a mass of 17,118 Da. Presumably, the shift to -1 also occurred because there was a paucity of the arginyl-tRNAArgucu. Introduction of a plasmid coding for the cognate tRNA for AGA and site directed mutagenesis prevented the formation of both frameshift species.
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PMID:Frameshift events associated with the lysyl-tRNA and the rare arginine codon, AGA, in Escherichia coli: a case study involving the human Relaxin 2 protein. 1847 30

This report describes an electrochemical biosensor for the detection of short DNA oligonucleotide of the avian flu virus H5N1 with sequence 5'-CCA AGC AAC AGA CTC AAA-3'. To fabricate this DNA biosensor, a gold (Au) electrode surface was modified with thiolated DNA probes with a sequence complementary to the target DNA. This modified Au electrode was incubated in a buffer solution containing the target DNA to form double-stranded DNA (ds-DNA) through hybridization. The ds-DNA on the electrode surface was then labeled with silver nanoparticles conjugated with a well-known DNA intercalator, doxorubicin. By performing cyclic voltammetry in an aqueous KCl solution (0.3M), the silver nanoparticle labels were detected as a result of the highly characteristic solid-state Ag/AgCl redox process. The signal obtained was subsequently used to quantify the amount of DNA. A detection limit of 1 pM has been achieved with this new DNA biosensor.
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PMID:A DNA biosensor based on the detection of doxorubicin-conjugated Ag nanoparticle labels using solid-state voltammetry. 1966 81

A novel hemoglobin variant was observed in pure sheep (Ovis aries) breeds of the island of Chios (Greece), Egypt and Hungary. This silent variant was identified by gel electrophoresis and RP-HPLC of dissociated globin chains. Two Arg for Lys substitutions were detected, by means of MALDI TOF electrospray mass spectrometric analysis for the intact globins, at positions beta66(E10) and beta144(HC1) of a globin chain having the sequence of the beta(B) chain. Sequencing of the beta-globin gene confirmed the variant gene as being an allele of the HBBB locus having the AAG-->AGG and the AAA-->AGA mutations at codons 66 and 144, respectively, both corresponding to the Lys-->Arg substitution. The intrinsic oxygen affinity of the variant Hb (logP(50)=0.79 at pH 7.0) was found to be intermediate between that of the sheep Hb B (logP(50)=0.92) and that of Cypriot mouflon (O. a. ophion) Hb (logP(50)=0.53), the latter having only the Lys-->Arg change at beta144, whereas nearly no differences were observed in the presence of the Cl(-) physiological effector. Result supports the indication that Arg at beta144 enhances the role of the ligand in decreasing oxygen affinity, this effect being partially counteracted when Arg is at beta66. Data also shows that the Lys-->Arg change at beta66 is responsible for 1.49 fold reduction in the intrinsic oxygen affinity. This hitherto undescribed variant increases to seven the number of alleles at the sheep HBBB locus. Following the nomenclature used for human Hb variants, the new allele was termed as the Hb Chios or [beta(B)66(E10) Lys-->Arg, 144(HC1)Lys-->Arg], whereas the proposed genetic nomenclature of the locus is HBBK.
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PMID:Structure and function of sheep hemoglobin Chios: A novel allele at the HBBB locus with two Lys-->Arg substitutions at positions beta66(E10) and beta144(HC1). 2048 81


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