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164Ile allele in the beta2-Adrenergic receptor gene is associated with risk of elevated blood pressure in women. The Copenhagen City Heart Study.

https://arctichealth.org/en/permalink/ahliterature173671
Source
Pharmacogenet Genomics. 2005 Sep;15(9):633-45
Publication Type
Article
Date
Sep-2005
Author
Amar A Sethi
Anne Tybjaerg-Hansen
Gorm B Jensen
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark.
Source
Pharmacogenet Genomics. 2005 Sep;15(9):633-45
Date
Sep-2005
Language
English
Publication Type
Article
Keywords
Alleles
Arginine - chemistry
Blood pressure
Body mass index
Denmark
Female
Gene Expression Regulation
Gene Frequency
Genetic Variation
Genotype
Glutamic Acid - chemistry
Glutamine - chemistry
Glycine - chemistry
Haplotypes
Heart rate
Heterozygote
Humans
Hypertension - genetics
Isoleucine - chemistry
Linkage Disequilibrium
Male
Receptors, Adrenergic, beta-2 - genetics
Risk
Risk factors
Sequence Analysis, DNA
Sex Factors
Time Factors
Abstract
Since beta2-adrenergic receptors are important regulators of blood pressure, genetic variation in this receptor could explain risk of elevated blood pressure in selected individuals. We tested the hypothesis that Gly16Arg, Gln27Glu, and Thr164Ile in the beta2-adrenergic receptor gene associated with elevated blood pressure.
We genotyped 9185 individuals from the adult Danish general population.
Allele frequencies of 16Arg, 27Glu, and 164Ile were 0.38, 0.44, and 0.01, respectively. Among women never treated with antihypertensive medication those heterozygous for Thr164Ile versus non-carriers had increased diastolic blood pressure (P=0.02). Women heterozygous for Thr164Ile versus non-carriers had an odds ratio for elevated blood pressure of 1.93 (95% CI: 1.30-2.86). Finally, women double heterozygous for Thr164Ile and Gln27Glu or Gly16Arg versus non-carriers at all 3 loci had an odds ratio for elevated blood pressure of 2.49 (1.28-4.85) or 3.19 (1.46-6.97). In men, blood pressure was not influenced by this genetic variation.
In women Thr164Ile heterozygosity is associated with increased diastolic blood pressure, and represent a risk factor for elevated blood pressure in women in the general population. This was most pronounced in those women also heterozygous for Gln27Glu or Gly16Arg.
PubMed ID
16041242 View in PubMed
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The basis of prostaglandin synthesis in coral: molecular cloning and expression of a cyclooxygenase from the Arctic soft coral Gersemia fruticosa.

https://arctichealth.org/en/permalink/ahliterature3964
Source
J Biol Chem. 2001 Mar 9;276(10):7033-40
Publication Type
Article
Date
Mar-9-2001
Author
R. Koljak
I. Järving
R. Kurg
W E Boeglin
K. Varvas
K. Valmsen
M. Ustav
A R Brash
N. Samel
Author Affiliation
Department of Bioorganic Chemistry, Institute of Chemistry, Tallinn Technical University, Akadeemia tee 15, Tallinn 12618, Estonia.
Source
J Biol Chem. 2001 Mar 9;276(10):7033-40
Date
Mar-9-2001
Language
English
Publication Type
Article
Keywords
Alanine - chemistry
Amino Acid Sequence
Animals
Arginine - chemistry
Blotting, Northern
COS Cells
Chromatography, Thin Layer
Cloning, Molecular
Cnidaria - metabolism
Cyclooxygenase 1
Cyclooxygenase 2
DNA, Complementary - metabolism
Hela Cells
Histidine - chemistry
Humans
Isoenzymes - chemistry
Isoleucine - chemistry
Membrane Proteins
Microscopy, Fluorescence
Models, Genetic
Molecular Sequence Data
Phylogeny
Plasmids - metabolism
Polymerase Chain Reaction
Prostaglandin-Endoperoxide Synthases - biosynthesis - chemistry - genetics
Prostaglandins - biosynthesis
Protein Binding
RNA, Messenger - metabolism
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Serine - chemistry
Tyrosine - chemistry
Abstract
In vertebrates, the synthesis of prostaglandin hormones is catalyzed by cyclooxygenase (COX)-1, a constitutively expressed enzyme with physiological functions, and COX-2, induced in inflammation and cancer. Prostaglandins have been detected in high concentrations in certain corals, and previous evidence suggested their biosynthesis through a lipoxygenase-allene oxide pathway. Here we describe the discovery of an ancestor of cyclooxygenases that is responsible for prostaglandin biosynthesis in coral. Using a homology-based polymerase chain reaction cloning strategy, the cDNA encoding a polypeptide with approximately 50% amino acid identity to both mammalian COX-1 and COX-2 was cloned and sequenced from the Arctic soft coral Gersemia fruticosa. Nearly all the amino acids essential for substrate binding and catalysis as determined in the mammalian enzymes are represented in coral COX: the arachidonate-binding Arg(120) and Tyr(355) are present, as are the heme-coordinating His(207) and His(388); the catalytic Tyr(385); and the target of aspirin attack, Ser(530). A key amino acid that determines the sensitivity to selective COX-2 inhibitors (Ile(523) in COX-1 and Val(523) in COX-2) is present in coral COX as isoleucine. The conserved Glu(524), implicated in the binding of certain COX inhibitors, is represented as alanine. Expression of the G. fruticosa cDNA afforded a functional cyclooxygenase that converted exogenous arachidonic acid to prostaglandins. The biosynthesis was inhibited by indomethacin, whereas the selective COX-2 inhibitor nimesulide was ineffective. We conclude that the cyclooxygenase occurs widely in the animal kingdom and that vertebrate COX-1 and COX-2 are evolutionary derivatives of the invertebrate precursor.
PubMed ID
11085996 View in PubMed
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Detection of familial defective apolipoprotein B-100 among patients clinically diagnosed with heterozygous familial hypercholesterolemia in maritime Canada.

https://arctichealth.org/en/permalink/ahliterature217613
Source
Clin Biochem. 1994 Aug;27(4):265-72
Publication Type
Article
Date
Aug-1994
Author
B. Morash
D L Guernsey
M H Tan
G. Dempsey
B A Nassar
Author Affiliation
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Source
Clin Biochem. 1994 Aug;27(4):265-72
Date
Aug-1994
Language
English
Publication Type
Article
Keywords
Adult
Aged
Apolipoprotein B-100
Apolipoproteins B - genetics - metabolism
Arginine - chemistry
Canada
Electrophoresis, Polyacrylamide Gel
Female
Gene Expression Regulation - genetics
Glutamine - chemistry
Heterozygote
Humans
Hyperlipoproteinemia Type II - diagnosis - genetics - metabolism
Male
Middle Aged
Mutation - genetics
Phenotype
Polymerase Chain Reaction
Receptors, LDL - genetics - metabolism
Restriction Mapping
Abstract
Familial defective apolipoprotein B-100 (FDB) is a genetic disorder resulting from a mutation in the apolipoprotein B-100 (apo B-100) gene, most frequently at position 3500, in which arginine is substituted for glutamine in the mature protein. This mutation drastically decreases the affinity of the mutant apo B-100 particle for the low-density lipoprotein (LDL) receptor, and hence decreases the clearance of cholesterol from the circulation. Familial hypercholesterolemia (FH), also a disorder of lipid metabolism, results from mutations in the gene for the LDL receptor. Both FDB and heterozygous FH occur at approximately the same frequency (1 in 500) among Caucasians and both produce clinical symptoms and signs that can be indistinguishable. Polymerase chain reaction (PCR) amplification and subsequent restriction analysis have been used to detect the substitution at codon 3500 in the apo B-100 gene using mutagenic PCR primers. At least one proband from 10 unrelated families with a history of hypercholesterolemia was screened by mutagenic PCR for FDB. Only one of 10 patients demonstrated the mutation for FDB. The mutant apo B-100 allele was shown to segregate with other clinically affected family members. These results demonstrate that molecular analysis is essential to distinguish between FDB and heterozygous FH in hypercholesterolemic families.
PubMed ID
8001287 View in PubMed
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Effect of L-arginine on Na+,K+-ATPase activity in rat aorta endothelium.

https://arctichealth.org/en/permalink/ahliterature9884
Source
Biochemistry (Mosc). 2002 Sep;67(9):1058-61
Publication Type
Article
Date
Sep-2002
Author
O V Akopova
O N Kharlamova
G L Vavilova
Author Affiliation
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kiev, 01024, Ukraine. circul@serv.biph.kiev.ua
Source
Biochemistry (Mosc). 2002 Sep;67(9):1058-61
Date
Sep-2002
Language
English
Publication Type
Article
Keywords
Animals
Aorta - drug effects - enzymology
Arginine - chemistry - pharmacology
Dose-Response Relationship, Drug
Endothelium, Vascular - drug effects - enzymology
Enzyme Activation
Enzyme Inhibitors - pharmacology
NG-Nitroarginine Methyl Ester - pharmacology
Na(+)-K(+)-Exchanging ATPase - antagonists & inhibitors - metabolism
Nitric Oxide - chemistry - metabolism
Nitric Oxide Synthase - antagonists & inhibitors
Nitroglycerin - chemistry - pharmacology
Rats
Rats, Wistar
Stereoisomerism
Structure-Activity Relationship
Abstract
The effect of L-arginine on the Na+,K+-ATPase activity in rat aorta endothelium was studied at its physiological concentrations in the range of 10(-6)-10(-3) M. The enzyme activity was 35.5% increased by low concentrations of L-arginine (
PubMed ID
12387723 View in PubMed
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Interaction of the lipoprotein lipase asparagine 291-->serine mutation with body mass index determines elevated plasma triacylglycerol concentrations: a study in hyperlipidemic subjects, myocardial infarction survivors, and healthy adults.

https://arctichealth.org/en/permalink/ahliterature54731
Source
J Lipid Res. 1995 Oct;36(10):2104-12
Publication Type
Article
Date
Oct-1995
Author
R M Fisher
F. Mailly
R E Peacock
A. Hamsten
M. Seed
J S Yudkin
U. Beisiegel
G. Feussner
G. Miller
S E Humphries
Author Affiliation
Department of Medicine, University College London Medical School, Rayne Institute, UK.
Source
J Lipid Res. 1995 Oct;36(10):2104-12
Date
Oct-1995
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Amino Acid Sequence
Arginine - chemistry
Base Sequence
Body mass index
Case-Control Studies
Female
Humans
Hyperlipidemia - blood - genetics
Lipoprotein Lipase - chemistry - genetics
Male
Middle Aged
Molecular Sequence Data
Mutation
Myocardial Infarction - blood - genetics - mortality
Research Support, Non-U.S. Gov't
Serine - chemistry
Survivors
Triglycerides - blood
Variation (Genetics)
Abstract
A mutation in the lipoprotein lipase (LPL) gene, resulting in the substitution of asparagine by serine at residue 291 (LPL-S291), was found to occur in young survivors of a myocardial infarction from Sweden, combined hyperlipidemic subjects from the United Kingdom, and type III hyperlipidemic subjects from Germany at allelic carrier frequencies no different from those found in companion healthy control subjects (3.63 vs. 3.37; 1.85 vs. 1.60; and 2.00 vs. 1.56%, respectively). In a group of 620 healthy middle-aged men from the United Kingdom with baseline and three subsequent annual lipid measurements, mean plasma triacylglycerol (TG), (but not plasma cholesterol) concentrations in carriers of the mutation were significantly elevated over non-carriers (1.95 vs. 1.61 mmol/l, P = 0.05, and 5.83 vs. 5.65 mmol/l, P = 0.29, respectively). When these healthy control subjects were divided according to tertiles of body mass index (BMI), as expected, non-carriers whose BMI was in the upper two tertiles (BMI > or = 25.0 kg/m2) had higher plasma TG concentrations than those in the lowest tertile (1.90 vs. 1.54 mmol/l), but this difference was much greater in LPL-S291 carriers (2.33 vs. 1.36 mmol/l, P = 0.01, BMI x genotype interaction, P = 0.02). To confirm this effect, a second group of 319 healthy subjects from the United Kingdom was screened for LPL-S291. The allelic frequency of the mutation was found to be 1.88% and the effect on plasma lipid concentrations was very similar to that observed in the first control group (plasma TG, 2.31 vs. 1.27 mmol/l, P or = 23.3 kg/m2) had higher plasma TG concentrations than non-carriers (2.31 vs. 1.42 mmol/l). Thus, the LPL-S291 variant may predispose individuals to elevated plasma TG concentrations under conditions such as increased BMI.
PubMed ID
8576637 View in PubMed
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Leptin receptor Lys109Arg and Gln223Arg polymorphisms are associated with early atherosclerosis.

https://arctichealth.org/en/permalink/ahliterature140455
Source
Metab Syndr Relat Disord. 2010 Oct;8(5):425-30
Publication Type
Article
Date
Oct-2010
Author
Meiju Saukko
Y Antero Kesäniemi
Olavi Ukkola
Author Affiliation
Institute of Clinical Medicine, Department of Internal Medicine and Biocenter Oulu, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland.
Source
Metab Syndr Relat Disord. 2010 Oct;8(5):425-30
Date
Oct-2010
Language
English
Publication Type
Article
Keywords
Adipocytes - cytology
Arginine - chemistry
Atherosclerosis - blood - genetics
Blood pressure
Body mass index
Endothelial Cells - cytology
Female
Glutamine - chemistry
Humans
Leptin - blood
Male
Middle Aged
Models, Genetic
Polymorphism, Genetic
Random Allocation
Receptors, Leptin - chemistry
Risk factors
Abstract
Leptin is a hormone expressed by the leptin gene, primarily in adipocytes, controlling food intake and energy expenditure. The effects of leptin are mediated by its receptor (LEPR) located in the central nervous system and other tissues, including adipocytes and endothelial cells. The aim of this study was to characterize two polymorphisms of LEPR, Lys109Arg (rs1137100) and Gln223Arg (rs1137101), as risk factors for early atherosclerosis. This connection has not been studied before.
This study was performed in the randomly selected, middle-aged control subjects (n=526) from our well-defined OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. Analysis of covariance (ANCOVA) was performed to study the associations between genotypes, intima media thickness (IMT) measurements, and risk factors for atherosclerosis.
Subjects with the genotype Lys109Arg had the lowest body mass index (BMI) (P?=?0.035), whereas Arg109Arg homozygotes had the highest total cholesterol (P=0.021) when adjusted for sex and age. Gln223Arg associated independently with systolic blood pressure (P=0.036). There were no differences in leptin concentrations between the genotypes. The adjusted (sex, age, BMI, smoking status, low-density lipoprotein cholesterol, systolic blood pressure, and fasting blood glucose) means for the IMT measurements were lowest in the Arg109 and Arg223 homozygotes (P=0.042 and P=0.041, ANCOVA, respectively).
The variations in the LEPR gene are independently associated with early atherosclerosis and some of its risk factors. These variations could possibly affect leptin signaling and thereby modify the effects of leptin on the atherosclerotic process.
PubMed ID
20874424 View in PubMed
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Sequence analysis of nuclear genes encoding functionally important complex I subunits in children with encephalomyopathy.

https://arctichealth.org/en/permalink/ahliterature29496
Source
J Mol Med. 2005 Oct;83(10):786-94
Publication Type
Article
Date
Oct-2005
Author
Reetta Hinttala
Johanna Uusimaa
Anne M Remes
Heikki Rantala
Ilmo E Hassinen
Kari Majamaa
Author Affiliation
Department of Neurology, University of Oulu, Finland.
Source
J Mol Med. 2005 Oct;83(10):786-94
Date
Oct-2005
Language
English
Publication Type
Article
Keywords
Alleles
Amino Acid Substitution
Arginine - chemistry - genetics
Child
Computational Biology
Conserved Sequence
Cysteine - chemistry - genetics
Electron Transport Complex I - deficiency - genetics
Humans
Mitochondrial Encephalomyopathies - enzymology - genetics
Mutation
NAD(P)H Dehydrogenase (Quinone) - deficiency - genetics
Protein Subunits - deficiency - genetics
Research Support, Non-U.S. Gov't
Sequence Analysis, DNA
Transcription, Genetic
Variation (Genetics)
Abstract
Complex I has a vital role in the energy production of the cell, and the clinical spectrum of complex I deficiency varies from severe lactic acidosis in infants to muscle weakness in adults. It has been estimated that the cause of complex I deficiency, especially in children, is often a mutation in the nuclear-encoded genes and, more rarely, in the genes encoded by mitochondrial DNA. We sequenced nine complex I subunit coding genes, NDUFAB1, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFV1 and NDUFV2, in 13 children with defined complex I deficiency. Two novel substitutions were found: a synonymous replacement 201A>T in NDUFV2 and a non-synonymous base exchange 52C>T in NDUFS8. The 52C>T substitution produced the replacement Arg18Cys in the leading peptide of the TYKY subunit. This novel missense mutation was found as a heterozygote in one patient and her mother, but not among 202 healthy controls nor among 107 children with undefined encephalomyopathy. Bioinformatic analyses suggested that Arg18Cys could lead to marked changes in the physicochemical properties of the mitochondrial-targeting peptide of TYKY, but we could not see changes in the assembly or activity of complex I or in the transcription of NDUFS8 in the fibroblasts of our patient. We suggest that Arg18Cys in the leading peptide of the TYKY subunit is not solely pathogenic, and that other genetic factors contribute to the disease-causing potential of this mutation.
PubMed ID
16142472 View in PubMed
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7 records – page 1 of 1.