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ß2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies.

https://arctichealth.org/en/permalink/ahliterature129736
Source
Eur Respir J. 2012 Mar;39(3):558-66
Publication Type
Article
Date
Mar-2012
Author
M. Thomsen
B G Nordestgaard
A A Sethi
A. Tybjærg-Hansen
M. Dahl
Author Affiliation
Dept of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark.
Source
Eur Respir J. 2012 Mar;39(3):558-66
Date
Mar-2012
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Asthma - epidemiology - genetics
Denmark - epidemiology
Female
Gene Frequency
Humans
Incidence
Lung - physiopathology
Male
Middle Aged
Polymorphism, Genetic
Prevalence
Pulmonary Disease, Chronic Obstructive - epidemiology - genetics
Receptors, Adrenergic, beta-2 - genetics
Young Adult
Abstract
The ß(2)-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone. We tested the hypothesis that three functional polymorphisms in the ADRB2 gene (Thr164Ile, Gly16Arg and Gln27Glu) are associated with reduced lung function, asthma or chronic obstructive pulmonary disease (COPD). We first genotyped 8,971 individuals from the Copenhagen City Heart Study for all three polymorphisms. To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism. We identified 60,910 Thr164Ile noncarriers, 1,822 heterozygotes and 16 homozygotes. In the Copenhagen City Heart Study, the Thr164Ile genotype was associated with reduced forced expiratory volume in 1 s (FEV(1)) % predicted (trend p = 0.01) and FEV(1)/forced vital capacity (FVC) (p = 0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV(1) % pred and FEV(1)/FVC, respectively, compared with noncarriers. The odds ratio for COPD in Thr164Ile heterozygotes was 1.46 (95% CI 1.05-2.02). In the Copenhagen General Population Study, the Thr164 genotype associated with reduced FEV(1) % pred (p = 0.04) and FEV(1)/FVC (p
PubMed ID
22075484 View in PubMed
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ß2 -adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66?750 individuals.

https://arctichealth.org/en/permalink/ahliterature131722
Source
J Intern Med. 2012 Mar;271(3):305-14
Publication Type
Article
Date
Mar-2012
Author
M. Thomsen
M. Dahl
A. Tybjaerg-Hansen
B G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
Source
J Intern Med. 2012 Mar;271(3):305-14
Date
Mar-2012
Language
English
Publication Type
Article
Keywords
Aged
Blood Pressure - genetics
Cross-Sectional Studies
Denmark
Female
Genetic Predisposition to Disease - genetics
Genotype
Humans
Hypertension - genetics
Male
Middle Aged
Muscle, Skeletal
Myocardial Ischemia - genetics
Myocytes, Smooth Muscle
Polymorphism, Single Nucleotide
Prospective Studies
Questionnaires
Receptors, Adrenergic, beta-2 - genetics
Sex Factors
Abstract
The ß(2) -adrenergic receptor (ADRB2) is located on smooth muscle cells and is an important regulator of smooth muscle tone. The Thr164Ile polymorphism (rs1800888) in the ADRB2 gene is rare but has profound functional consequences on receptor function and could cause lifelong elevated smooth muscle tone. We tested the hypothesis that Thr164Ile is associated with increased blood pressure, increased frequency of hypertension and increased risk of cardiovascular disease (CVD).
A total of 66 750 individuals from two large Danish general population studies were genotyped, and 1943 Thr164Ile heterozygotes and 16 homozygotes were identified.
Thr164Ile genotype was associated with increased systolic and diastolic blood pressure in women (trend: P = 0.04 and 0.02): systolic and diastolic blood pressure increased by 5% and 2%, respectively, in female homozygotes compared with female noncarriers. All female Thr164Ile homozygotes had hypertension compared with 58% of female heterozygotes and 54% of female noncarriers (chi-square: P = 0.001). Female Thr164Ile homozygotes and heterozygotes had odds ratios for ischaemic heart disease (IHD) of 2.93 (0.56-15.5) and 1.28 (1.03-1.61), respectively, compared with female noncarriers (trend: P = 0.007). These differences were not observed in men. Furthermore, Gly16Arg (rs1042713) and Gln27Glu (rs1042714) in the ADRB2 gene were not associated with blood pressure, hypertension or CVD either in the population overall or in women and men separately.
ADRB2 Thr164Ile is associated with increased blood pressure, increased frequency of hypertension and increased risk of IHD amongst women in the general population. These findings, particularly for homozygotes, are novel.
PubMed ID
21883537 View in PubMed
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ß2-adrenergic receptor Thr164Ile polymorphism, obesity, and diabetes: comparison with FTO, MC4R, and TMEM18 polymorphisms in more than 64,000 individuals.

https://arctichealth.org/en/permalink/ahliterature125626
Source
J Clin Endocrinol Metab. 2012 Jun;97(6):E1074-9
Publication Type
Article
Date
Jun-2012
Author
Mette Thomsen
Morten Dahl
Anne Tybjærg-Hansen
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Source
J Clin Endocrinol Metab. 2012 Jun;97(6):E1074-9
Date
Jun-2012
Language
English
Publication Type
Article
Keywords
Adult
Body mass index
Cohort Studies
Denmark - epidemiology
Diabetes Mellitus - epidemiology - genetics
Female
Genetic Predisposition to Disease - epidemiology - genetics
Genotype
Humans
Male
Membrane Proteins - genetics
Obesity - epidemiology - genetics
Polymorphism, Single Nucleotide - genetics
Proteins - genetics
Receptor, Melanocortin, Type 4 - genetics
Receptors, Adrenergic, beta-2 - genetics
Risk factors
Abstract
The ß(2)-adrenergic receptor (ADRB2) influences regulation of energy balance by stimulating catecholamine-induced lipolysis in adipose tissue. The rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence risk of obesity and subsequently diabetes.
We tested the hypothesis that the ADRB2rs1800888(Thr164Ile) polymorphism associates with risk of obesity and diabetes and compared effect sizes with those of FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238).
We conducted a population-based cohort study in Copenhagen, Denmark.
We genotyped more than 64,000 individuals from the Danish general population.
We evaluated body mass index (BMI), obesity (BMI =30 kg/m(2)), and diabetes.
Rare allele frequencies were 0.02 for T for ADRB2rs1800888(Thr164Ile), 0.40 for A for FTOrs9939609, 0.25 for C for MC4Rrs17782313, and 0.20 for T for TMEM18rs6548238. For rare vs. common homozygotes, odds ratio for obesity was 3.32 (95% confidence interval = 1.08-10.19) for ADRB2rs1800888(Thr164Ile), 1.42 (1.35-1.52) for FTOrs9939609, 1.18 (1.06-1.30) for MC4Rrs17782313, and 1.28 (1.10-1.50) for TMEM18rs6548238 (common vs. rare). Corresponding odds ratios for diabetes were 1.85 (0.24-14.29), 1.22 (1.07-1.39), 0.96 (0.80-1.16), and 1.61 (1.17-2.22), respectively. After adjustment for BMI, only TMEM18rs6548238 remained associated with diabetes. BMI was increased in rare vs. common homozygotes in FTOrs9939609, MC4Rrs17782313, and TMEM18rs6548238 (common vs. rare) but not in ADRB2rs1800888(Thr164Ile).
Our results suggest that ADRB2rs1800888(Thr164Ile) rare vs. common homozygotes are not significantly associated with an increase in BMI measured continuously but may be associated with an increased risk of obesity. Also, TMEM18rs6548238 associated with risk of diabetes after adjustment for BMI. These findings need confirmation in other studies.
PubMed ID
22466342 View in PubMed
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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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Beta2-adrenergic receptor allele frequencies in the Quechua, a high altitude native population.

https://arctichealth.org/en/permalink/ahliterature195397
Source
Ann Hum Genet. 2000 Mar;64(Pt 2):135-43
Publication Type
Article
Date
Mar-2000
Author
J L Rupert
M V Monsalve
D V Devine
P W Hochachka
Author Affiliation
Department of Zoology, University of British Columbia, Vancouver, Canada. rupert@zoology.ubc.ca
Source
Ann Hum Genet. 2000 Mar;64(Pt 2):135-43
Date
Mar-2000
Language
English
Publication Type
Article
Keywords
Alleles
Altitude
Base Sequence
DNA Primers
Gene Frequency
Humans
Indians, South American - genetics
Linkage Disequilibrium
Peru
Polymorphism, Genetic
Receptors, Adrenergic, beta-2 - genetics
Abstract
The beta2-adrenergic receptor is involved in the control of numerous physiological processes and, as the primary catecholamine receptor in the lungs, is of particular importance in the regulation of pulmonary function. There are several polymorphic loci in the beta2-adrenergic receptor gene that have alleles that alter receptor function, including two (A/G46, G/C79) that increase agonist sensitivity. As such a phenotype may increase vaso and bronchial dilation, thereby facilitating air and blood flow through the lungs, we hypothesized that selection may have favoured these alleles in high altitude populations as part of an adaptive strategy to deal with the hypoxic conditions characteristic of such environments. We tested this hypothesis by determining the allele frequencies for these two polymorphisms, as well one additional missense mutation (C/T491) and two silent mutations (G/A252 and C/A523) in 63 Quechua speaking natives from communities located between 3200 and 4200 m on the Peruvian altiplano. These frequencies were compared with those of two lowland populations, one native American (Na-Dene from the west coast of Canada) and one Caucasian of Western European descent. The Quechua manifest many of the pulmonary characteristics of high altitude populations and differences in allele frequencies between the Quechua and lowlanders could be indicative of a selective advantage conferred by certain genotypes in high altitude environments. Allele frequencies varied between populations at some loci and patterns of linkage disequilibrium differed between the old-world and new-world samples; however, as these populations are not closely related, significant variation would be expected due to stochastic effects alone. Neither of the alleles associated with increased receptor sensitivity (A46, G79) was significantly over-represented in the Quechua compared with either lowland group. The Quechua were monomorphic for the C allele at base 79. This variant has been associated with body mass index; however no clearly defined metabolic phenotype has been established. In addition, we sequenced the coding region of the gene in three unrelated Quechua to determine if there were any other polymorphisms common in this population. None were detected.
PubMed ID
11246467 View in PubMed
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beta2-adrenergic receptor gene single-nucleotide polymorphisms are associated with rheumatoid arthritis in northern Sweden.

https://arctichealth.org/en/permalink/ahliterature13757
Source
Scand J Rheumatol. 2004;33(6):395-8
Publication Type
Article
Date
2004
Author
B. Xu
L. Arlehag
S-B Rantapää-Dahlquist
A K Lefvert
Author Affiliation
Department of Immunology, American Red Cross Biomedical Research and Development, MD 20855, USA. xubiy@usa.redcross.org
Source
Scand J Rheumatol. 2004;33(6):395-8
Date
2004
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alleles
Arthritis, Rheumatoid - diagnosis - epidemiology - genetics
Base Sequence
Case-Control Studies
Cohort Studies
Comparative Study
Confidence Intervals
Female
Gene Expression Regulation
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Molecular Sequence Data
Odds Ratio
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Probability
Prognosis
Receptors, Adrenergic, beta-2 - genetics
Reference Values
Research Support, Non-U.S. Gov't
Sensitivity and specificity
Severity of Illness Index
Sweden - epidemiology
Abstract
The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein-coupled receptors and is present on skeletal and cardiac muscle cells and on lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population and the distributions of single-nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164 are changed in asthma, obesity, and hypertension and in the autoimmune disease myasthenia gravis. An involvement of the beta2-AR has also been suggested in human rheumatoid arthritis (RA) and its animal model. We describe here an increased prevalence of the alleles Arg16 and Gln27 and a lower prevalence of homozygosis for Gly16 and Glu27 in patients with RA. Patients having the genotype combination GlyGly16-GlnGlu27 had higher levels of rheumatoid factor (RF) and a more active disease than other patients. Patients having the genotype Arg16-Gln27+ had higher levels of RF when compared to those having Arg16+Gln27+, and patients who were carriers of Gln27 had a more active disease than non-carriers of Gln27. Our results show an association of beta2-AR SNPs with RA in a population from the northern part of Sweden. Our study also confirms the strong linkage disequilibrium of genotypes at amino acid positions 16 and 27.
PubMed ID
15794198 View in PubMed
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Beta(2)-adrenergic receptor gene variation and hypertension in subjects with type 2 diabetes.

https://arctichealth.org/en/permalink/ahliterature47718
Source
Hypertension. 2001 May;37(5):1303-8
Publication Type
Article
Date
May-2001
Author
K. Bengtsson
M. Orho-Melander
O. Melander
U. Lindblad
J. Ranstam
L. Råstam
L. Groop
Author Affiliation
Department of Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden. kristina.a.bengtsson@vgregion.se
Source
Hypertension. 2001 May;37(5):1303-8
Date
May-2001
Language
English
Publication Type
Article
Keywords
Aged
Analysis of Variance
Arginine - genetics
Case-Control Studies
Diabetes Mellitus, Type 2 - complications - genetics
Female
Genotype
Glutamic Acid - genetics
Glutamine - genetics
Glycine - genetics
Humans
Hypertension - complications - genetics
Male
Middle Aged
Polymorphism, Genetic
Receptors, Adrenergic, beta-2 - genetics
Research Support, Non-U.S. Gov't
Variation (Genetics)
Abstract
The aim of this study was to investigate whether polymorphisms in the beta(2)-adrenergic receptor gene (5'LC-Arg19Cys, Arg16Gly, Gln27Glu) are associated with hypertension in patients with or without type 2 diabetes and with the blood pressure levels in normotensive sib pairs. The association study included 291 hypertensive patients without type 2 diabetes, 124 hypertensive patients with type 2 diabetes, and 265 healthy control subjects from SWEDEN: In addition, normotensive sib pairs that were discordant for the Arg16Gly (72 pairs) and Gln27Glu (40 pairs) polymorphisms were identified in type 2 diabetes families from FINLAND: Genotyping was performed using polymerase chain reaction-restriction fragment-length polymorphism analysis. Homozygous carriers of the Arg16 allele had a significantly increased odds ratio (OR) for hypertension in patients with type 2 diabetes (OR 2.14; 95% confidence interval [CI], 1.05 to 4.33), particularly among lean (body mass index
PubMed ID
11358945 View in PubMed
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beta2 Adrenoceptor gene single nucleotide polymorphisms are associated with rheumatoid arthritis in northern Sweden.

https://arctichealth.org/en/permalink/ahliterature13779
Source
Ann Rheum Dis. 2005 May;64(5):773-6
Publication Type
Article
Date
May-2005
Author
B-Y Xu
L. Arlehag
S-B Rantapää-Dahlquist
A K Lefvert
Author Affiliation
Immunological Research Laboratory, Center for Molecular Medicine and Department of Medicine, Karolinska Institutet, S-171 76 Stockholm, Sweden.
Source
Ann Rheum Dis. 2005 May;64(5):773-6
Date
May-2005
Language
English
Publication Type
Article
Keywords
Arthritis, Rheumatoid - blood - genetics
Carrier state
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Linkage Disequilibrium
Male
Polymerase Chain Reaction - methods
Polymorphism, Single Nucleotide
Receptors, Adrenergic, beta-2 - genetics
Research Support, Non-U.S. Gov't
Rheumatoid Factor - blood
Sweden
Abstract
BACKGROUND: beta(2) Adrenoceptor (beta(2)-AR) represents a link between the sympathetic nervous system and the immune system, and may be involved in human rheumatoid arthritis (RA). The gene encoding beta(2)-AR contains three single nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164. OBJECTIVE: To examine the common variants at positions 16 and 27 and their association with RA. METHODS: An allele-specific polymerase chain reaction to determine the common variants at positions 16 and 27 was used in 154 patients with RA and 198 ethnically matched healthy subjects from northern Sweden. RESULTS: Carriage of Arg16 and of Gln27 was associated with RA. Carriage of Gln27 was associated with activity of the disease and in combination with non-carriage of Arg16 with higher levels of rheumatoid factor. CONCLUSION: The beta2-AR SNPs may thus constitute an additional non-major histocompatibility complex association in RA.
PubMed ID
15498794 View in PubMed
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A common beta2-adrenoceptor gene haplotype protects against obesity in Swedish women.

https://arctichealth.org/en/permalink/ahliterature171956
Source
Obes Res. 2005 Oct;13(10):1645-50
Publication Type
Article
Date
Oct-2005
Author
Hong Jiao
Ingrid Dahlman
Per Eriksson
Juha Kere
Peter Arner
Author Affiliation
Department of Biosciences at Novum, Karolinska Institutet, Stockholm, Sweden.
Source
Obes Res. 2005 Oct;13(10):1645-50
Date
Oct-2005
Language
English
Publication Type
Article
Keywords
Adult
Base Sequence
DNA Primers
Female
Haplotypes
Humans
Middle Aged
Obesity - genetics - prevention & control
Receptors, Adrenergic, beta-2 - genetics
Sweden
Abstract
The beta2-adrenoceptor gene may be of particular importance for human obesity because catecholamines have a central role in energy expenditure both as neurotransmitters and hormones. The gene is highly polymorphic, and individual polymorphisms have previously been examined for their relationship to obesity, but results are conflicting. We performed a haplotype analysis of the beta2-adrenoceptor gene in 1354 women and 421 men, all healthy and at least second generation Scandinavian and with a large interindividual variation in body fat mass. We found three common haplotypes. One of these haplotypes, identified as T, A, C, C at nucleotide positions -47, 46, 79, and 491, was in its homozygote form more common among lean (18%) than obese (13%) women (p = 0.0028), but there was no association with obesity in men (p = 0.47). Women who were homozygous for this haplotype had lower BMI (p = 0.009) and percentage body fat (p = 0.005) in comparison with those having other haplotypes or being heterozygous for TACC. The data suggest an important role of the beta2-adrenoceptor gene in obesity because a common haplotype has recessive protective effects against excess body fat, at least in women.
PubMed ID
16286511 View in PubMed
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20 records – page 1 of 2.