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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
Less detail

The ABCG5/8 cholesterol transporter and myocardial infarction versus gallstone disease.

https://arctichealth.org/en/permalink/ahliterature104661
Source
J Am Coll Cardiol. 2014 May 27;63(20):2121-8
Publication Type
Article
Date
May-27-2014
Author
Stefan Stender
Ruth Frikke-Schmidt
Børge G Nordestgaard
Anne Tybjaerg-Hansen
Author Affiliation
Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Source
J Am Coll Cardiol. 2014 May 27;63(20):2121-8
Date
May-27-2014
Language
English
Publication Type
Article
Keywords
ATP-Binding Cassette Transporters - blood - genetics
Aged
Denmark - epidemiology
Female
Gallstones - blood - epidemiology - genetics
Genetic Variation
Genotype
Humans
Lipoproteins - blood - genetics
Male
Middle Aged
Myocardial Infarction - blood - epidemiology - genetics
Prevalence
Abstract
The study sought to test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, may simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction (MI) and gallstone disease in opposite directions.
High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation.
A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI and 3,174 with symptomatic gallstone disease. Subjects were genotyped for 6 common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated.
Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5.9% (0.20 mmol/l) for individuals with a score =8.0 (prevalence = 11%) versus
Notes
Comment In: J Am Coll Cardiol. 2014 May 27;63(20):2129-3024657684
PubMed ID
24657701 View in PubMed
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ADH1B and ADH1C genotype, alcohol consumption and biomarkers of liver function: findings from a Mendelian randomization study in 58,313 European origin Danes.

https://arctichealth.org/en/permalink/ahliterature268417
Source
PLoS One. 2014;9(12):e114294
Publication Type
Article
Date
2014
Author
Debbie A Lawlor
Marianne Benn
Luisa Zuccolo
N Maneka G De Silva
Anne Tybjaerg-Hansen
George Davey Smith
Børge G Nordestgaard
Source
PLoS One. 2014;9(12):e114294
Date
2014
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alcohol Dehydrogenase - genetics
Alcohol Drinking - epidemiology - genetics - physiopathology
Denmark - epidemiology
Female
Genetic Variation
Genotype
Humans
Liver - metabolism - physiopathology
Male
Mendelian Randomization Analysis
Middle Aged
Abstract
The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol.
We used variants in ADH1B and ADH1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), ?-glutamyl-transferase (?-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56).
In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (-4.5, 11.9) from genetic-IV analyses] and ?-GT [8.2% (7.8, 8.5) and 6.8% (-2.8, 16.5)]. The point estimates from the two methods were very similar and statistically the results from the two methods were consistent with each other for effects with ALT and ?-GT (both pdiff>0.3). Results from the multivariable analyses suggested a weak inverse association of alcohol with ALP [-1.5% (-1 .7, -1.3)], which differed from the strong positive effect found in genetic-IV analyses [11.6% (6.8, 16.4)] (p diff
Notes
Cites: Addiction. 2000 Feb;95(2):251-6510723854
Cites: Hum Genet. 2000 Jun;106(6):589-9310942105
Cites: Clin Liver Dis. 2000 Feb;4(1):115-31, vii11232180
Cites: Am J Hum Genet. 2001 Jul;69(1):1-1411410837
Cites: Metabolism. 2003 Sep;52(9):1096-10114506613
Cites: Clin Chem. 2004 Feb;50(2):443-614752018
Cites: Liver. 1989 Aug;9(4):189-972671569
Cites: Lancet. 1993 Mar 27;341(8848):837-88096045
Cites: Recent Dev Alcohol. 1995;12:163-797624539
Cites: Hepatology. 1996 May;23(5):1025-98621128
Cites: Environ Health Perspect. 1996 May;104 Suppl 3:563-78781384
Cites: Am J Gastroenterol. 1998 Nov;93(11):2022-369820369
Cites: Alcohol Clin Exp Res. 1999 Apr;23(4):751-610235313
Cites: Alcohol Res Health. 2006;29(4):245-5417718403
Cites: PLoS Med. 2007 Dec;4(12):e35218076282
Cites: Stat Med. 2008 Apr 15;27(8):1133-6317886233
Cites: Hum Mol Genet. 2009 Feb 1;18(3):580-9318996923
Cites: Hypertension. 2009 Jul;54(1):84-9019470880
Cites: Am J Gastroenterol. 2009 Sep;104(9):2182-819550411
Cites: Hum Mol Genet. 2009 Nov 15;18(22):4457-6619687126
Cites: J Intern Med. 2011 May;269(5):525-3721210875
Cites: Biol Psychiatry. 2011 Sep 15;70(6):504-1221497796
Cites: Hum Genet. 2012 Aug;131(8):1361-7422476623
Cites: Int J Epidemiol. 2012 Oct;41(5):1383-9323045203
Cites: Eur Heart J. 2013 Aug;34(32):2519-2823492672
PubMed ID
25503943 View in PubMed
Less detail

Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts.

https://arctichealth.org/en/permalink/ahliterature108601
Source
BMJ. 2013;347:f4262
Publication Type
Article
Date
2013
Author
Tom M Palmer
Børge G Nordestgaard
Marianne Benn
Anne Tybjærg-Hansen
George Davey Smith
Debbie A Lawlor
Nicholas J Timpson
Author Affiliation
Division of Health Sciences, Warwick Medical School, University of Warwick, Warwick, UK.
Source
BMJ. 2013;347:f4262
Date
2013
Language
English
Publication Type
Article
Keywords
Adult
Aged
Blood Pressure - genetics
Body mass index
Denmark
Female
Humans
Hyperuricemia - etiology - genetics
Male
Mendelian Randomization Analysis
Middle Aged
Myocardial Ischemia - blood - genetics
Prospective Studies
Regression Analysis
Uric Acid - blood
Abstract
To assess the associations between both uric acid levels and hyperuricaemia, with ischaemic heart disease and blood pressure, and to explore the potentially confounding role of body mass index.
Mendelian randomisation analysis, using variation at specific genes (SLC2A9 (rs7442295) as an instrument for uric acid; and FTO (rs9939609), MC4R (rs17782313), and TMEM18 (rs6548238) for body mass index).
Two large, prospective cohort studies in Denmark.
We measured levels of uric acid and related covariables in 58,072 participants from the Copenhagen General Population Study and 10,602 from the Copenhagen City Heart Study, comprising 4890 and 2282 cases of ischaemic heart disease, respectively.
Blood pressure and prospectively assessed ischaemic heart disease.
Estimates confirmed known observational associations between plasma uric acid and hyperuricaemia with risk of ischaemic heart disease and diastolic and systolic blood pressure. However, when using genotypic instruments for uric acid and hyperuricaemia, we saw no evidence for causal associations between uric acid, ischaemic heart disease, and blood pressure. We used genetic instruments to investigate body mass index as a potentially confounding factor in observational associations, and saw a causal effect on uric acid levels. Every four unit increase of body mass index saw a rise in uric acid of 0.03 mmol/L (95% confidence interval 0.02 to 0.04), and an increase in risk of hyperuricaemia of 7.5% (3.9% to 11.1%).
By contrast with observational findings, there is no strong evidence for causal associations between uric acid and ischaemic heart disease or blood pressure. However, evidence supports a causal effect between body mass index and uric acid level and hyperuricaemia. This finding strongly suggests body mass index as a confounder in observational associations, and suggests a role for elevated body mass index or obesity in the development of uric acid related conditions.
Notes
Cites: Stroke. 2006 Jun;37(6):1503-716675740
Cites: JAMA. 2000 May 10;283(18):2404-1010815083
Cites: Ann Epidemiol. 2007 Jul;17(7):511-317466535
Cites: JAMA. 2007 Jul 18;298(3):299-30817635890
Cites: J Am Coll Cardiol. 2007 Nov 27;50(22):2173-9518036459
Cites: Am J Hum Genet. 2008 Jan;82(1):139-4918179892
Cites: Clin Chem. 2008 Feb;54(2):273-8418039719
Cites: Nat Genet. 2008 Apr;40(4):437-4218327257
Cites: Hypertension. 2006 Dec;48(6):1031-617060508
Cites: J Rheumatol. 2010 Feb;37(2):410-620032099
Cites: Genomics. 2000 Jun 1;66(2):217-2010860667
Cites: Hypertension. 2001 Mar;37(3):875-8111244011
Cites: Int J Epidemiol. 2003 Feb;32(1):1-2212689998
Cites: Hypertension. 2003 Jun;41(6):1183-9012707287
Cites: Curr Med Res Opin. 2004 Mar;20(3):369-7915025846
Cites: Int J Epidemiol. 2004 Feb;33(1):30-4215075143
Cites: Proc Natl Acad Sci U S A. 1981 Nov;78(11):6858-626947260
Cites: J Mol Evol. 1992 Jan;34(1):78-841556746
Cites: Ann Intern Med. 1999 Jul 6;131(1):7-1310391820
Cites: Epidemiology. 1999 Jul;10(4):391-710401873
Cites: Hypertension. 2005 Jan;45(1):28-3315569852
Cites: Stat Med. 2005 Oct 15;24(19):2911-3516152135
Cites: N Engl J Med. 2005 Dec 8;353(23):2450-6116339094
Cites: Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1186-9218356554
Cites: Diabetes Care. 2008 Aug;31(8):1662-718487473
Cites: PLoS Med. 2008 Oct 7;5(10):e19718842065
Cites: Lancet. 2009 Mar 28;373(9669):1083-9619299006
Cites: Hypertension. 2009 Jul;54(1):84-9019470880
Cites: Arthritis Care Res (Hoboken). 2010 Feb;62(2):170-8020191515
Cites: Int J Epidemiol. 2010 Jun;39(3):907-1820348110
Cites: Int J Clin Pract. 2010 Jun;64(7):900-720584223
Cites: Kidney Int. 2010 Sep;78(5):446-5220613716
Cites: Nat Genet. 2010 Nov;42(11):937-4820935630
Cites: Circ Cardiovasc Genet. 2010 Dec;3(6):523-3020884846
Cites: Int J Obes (Lond). 2011 Feb;35(2):300-820714329
Cites: N Engl J Med. 2011 Feb 24;364(8):719-2921345101
Cites: Kidney Int. 2012 Mar;81(5):502-722189840
Cites: PLoS Med. 2012;9(5):e100121222563304
Cites: PLoS One. 2012;7(6):e3932122723994
Cites: BMJ. 2012;345:e732523131671
Cites: Arthritis Rheum. 2009 Jul 15;61(7):885-9219565556
Cites: PLoS One. 2009;4(11):e772919890391
Comment In: Rev Clin Esp. 2014 Jan-Feb;214(1):48
PubMed ID
23869090 View in PubMed
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Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study.

https://arctichealth.org/en/permalink/ahliterature15007
Source
Respir Res. 2005;6(1):113
Publication Type
Article
Date
2005
Author
Morten Dahl
Anne Tybjaerg-Hansen
Peter Lange
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev University Hospital, DK-2730 Herlev, Denmark. dahlos2003@yahoo.dk
Source
Respir Res. 2005;6(1):113
Date
2005
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Asthma - epidemiology - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Denmark - epidemiology
Female
Genetic Predisposition to Disease - epidemiology - genetics
Genetic Screening - methods
Genetics, Population
Heterozygote
Humans
Incidence
Introns - genetics
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive - epidemiology - genetics
Research Support, Non-U.S. Gov't
Risk Assessment - methods
Risk factors
Women
Abstract
BACKGROUND: Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD). METHODS: We genotyped 9131 individuals from the adult Danish population for cystic fibrosis 5T, 7T, 9T, and F508del alleles, and examined associations between 11 different genotype combinations, and annual FEV1 decline and risk of asthma or COPD. RESULTS: 5T heterozygotes vs. 7T homozygous controls had no increase in annual FEV1 decline, self-reported asthma, spirometry-defined COPD, or incidence of hospitalization from asthma or COPD. In 5T/7T heterozygotes vs. 7T homozygous controls we had 90% power to detect an increase in FEV1 decline of 8 ml, an odds ratio for self-reported asthma and spirometry-defined COPD of 1.9 and 1.7, and a hazard ratio for asthma and COPD hospitalization of 1.8 and 1.6, respectively. Both 5T homozygotes identified in the study showed evidence of asthma, while none of four 5T/F508del compound heterozygotes had severe pulmonary disease. 7T/9T individuals had annual decline in FEV1 of 19 ml compared with 21 ml in 7T homozygous controls (t-test: P = 0.03). 6.7% of 7T homozygotes without an F508del allele in the cystic fibrosis transmembrane conductance regulator gene reported asthma vs. 11% of 7T/9T individuals with an F508del allele (chi2: P = 0.01) and 40% of 7T homozygotes with an F508del allele (P = 0.04). 7T homozygotes with vs. without an F508del allele also had higher incidence of asthma hospitalization (log-rank: P = 0.003); unadjusted and adjusted equivalent hazard ratios for asthma hospitalization were 11 (95%CI: 1.5-78) and 6.3 (0.84-47) in 7T homozygotes with vs. without an F508del allele. CONCLUSION: Polythymidine 5T heterozygosity is not associated with pulmonary dysfunction or disease in the adult Caucasian population. Furthermore, our results support that F508del heterozygosity is associated with increased asthma risk independently of the 5T allele.
PubMed ID
16212675 View in PubMed
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AT1 mutations and risk of atrial fibrillation based on genotypes from 71,000 individuals from the general population.

https://arctichealth.org/en/permalink/ahliterature118425
Source
Br J Clin Pharmacol. 2013 Jul;76(1):114-24
Publication Type
Article
Date
Jul-2013
Author
Sarah C W Marott
Børge G Nordestgaard
Gorm B Jensen
Anne Tybjaerg-Hansen
Marianne Benn
Author Affiliation
Department of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark.
Source
Br J Clin Pharmacol. 2013 Jul;76(1):114-24
Date
Jul-2013
Language
English
Publication Type
Article
Keywords
Aged
Atrial Fibrillation - genetics
Denmark
Female
Genetic Predisposition to Disease
Genetic Variation
Genotype
Heterozygote
Humans
Male
Middle Aged
Mutation
Prospective Studies
Receptor, Angiotensin, Type 1 - genetics
Risk
Sex Factors
Abstract
Activation of the angiotensin?II type?1 (AT1 ) receptor has been shown to mediate the structural and electrical remodelling of the atrial myocardium associated with atrial fibrillation. We hypothesized that AT1 genotypic variation is associated with atrial fibrillation or diseases predisposing to atrial fibrillation, such as hypertension, heart failure, ischaemic heart disease and myocardial infarction, in the general population.
We resequenced the AT1 gene in 760 individuals with atrial fibrillation and identified two nonsynonymous variants (I103T and A244S), which were subsequently genotyped in the prospective Copenhagen City Heart Study (n = 10?603) and the prospective Copenhagen General Population Study (n = 60?647).
Risk of atrial fibrillation for heterozygotes for AT1 genetic variants A244S and I103T/A244S vs. noncarriers was increased by 2.7-fold (95% confidence interval 1.5- to 5.1-fold) and 2.6-fold (95% confidence interval 1.6- to 4.2-fold), respectively, for men.
Heterozygosity for the nonsynonymous AT1 genetic variants A244S and I103T/A244S was associated with increased risk of atrial fibrillation in men. The AT1 recptor might be a target for the pharmaceutical industry. This finding needs to be validated in independent studies.
Notes
Cites: J Electrocardiol. 2010 Jul-Aug;43(4):373-719932491
Cites: J Am Coll Cardiol. 2010 May 25;55(21):2299-30720488299
Cites: Europace. 2011 Mar;13(3):346-5421076147
Cites: J Am Coll Cardiol. 2011 Mar 15;57(11):e101-9821392637
Cites: Europace. 2011 Apr;13(4):451-221385772
Cites: Br J Pharmacol. 2011 Nov;164 Suppl 1:S1-32422040146
Cites: J Renin Angiotensin Aldosterone Syst. 2011 Dec;12(4):549-5621436211
Cites: J Hum Hypertens. 2012 Oct;26(10):563-922129612
Cites: J Am Coll Cardiol. 2000 May;35(6):1669-7710807475
Cites: Circulation. 2000 Jun 13;101(23):2678-8110851203
Cites: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7615-2010852946
Cites: Mol Pharmacol. 2001 Jul;60(1):1-1911408595
Cites: Trends Endocrinol Metab. 2002 Oct;13(8):336-4312217490
Cites: Nucleic Acids Res. 2003 Jan 1;31(1):334-4112520017
Cites: Nucleic Acids Res. 2003 Jul 1;31(13):3812-412824425
Cites: Am J Cardiol. 2003 Dec 15;92(12):1419-2314675577
Cites: Circulation. 2004 Apr 6;109(13):1640-615023884
Cites: Nature. 1996 Sep 26;383(6598):347-508848049
Cites: Science. 1996 Nov 1;274(5288):768-708864113
Cites: EMBO J. 1997 Nov 17;16(22):6737-479362488
Cites: Ann Intern Med. 2012 Jan 3;156(1 Pt 1):69; author reply 7022213505
Cites: Dan Med Bull. 1999 Sep;46(4):354-710514943
Cites: Eur Heart J. 2006 Mar;27(5):512-816311236
Cites: Nat Clin Pract Cardiovasc Med. 2006 May;3(5):276-8216645668
Cites: Mol Endocrinol. 2006 May;20(5):953-7016141358
Cites: Biochim Biophys Acta. 2007 Apr;1768(4):794-80717188232
Cites: JAMA. 2007 Jul 18;298(3):299-30817635890
Cites: J Am Coll Cardiol. 2007 Nov 27;50(22):2173-9518036459
Cites: Pharmacogenet Genomics. 2008 Jun;18(6):525-3318496132
Cites: J Mol Cell Cardiol. 2009 Jan;46(1):15-2418848837
Cites: Kardiologiia. 2010;50(6):27-3420659024
PubMed ID
23210602 View in PubMed
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Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency: the Copenhagen City Heart Study.

https://arctichealth.org/en/permalink/ahliterature53601
Source
Circulation. 2003 Feb 11;107(5):747-52
Publication Type
Article
Date
Feb-11-2003
Author
Morten Dahl
Anne Tybjaerg-Hansen
Henrik Sillesen
Gorm Jensen
Rolf Steffensen
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev University Hospital, Denmark.
Source
Circulation. 2003 Feb 11;107(5):747-52
Date
Feb-11-2003
Language
English
Publication Type
Article
Keywords
Adult
Age Distribution
Aged
Aged, 80 and over
Blood Pressure - genetics
Brain ischemia - epidemiology
Comorbidity
Denmark - epidemiology
Female
Gene Frequency
Genetic Screening
Genotype
Homozygote
Humans
Logistic Models
Male
Middle Aged
Myocardial Ischemia - epidemiology
Odds Ratio
Polymorphism, Genetic
Reference Values
Research Support, Non-U.S. Gov't
Risk assessment
alpha 1-Antitrypsin Deficiency - epidemiology - genetics
Abstract
BACKGROUND: Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity. METHODS AND RESULTS: We genotyped 7963 control subjects from the adult general population of Denmark, 1131 Danish patients with ICVD, and 2221 Danish patients with IHD. Compared with MM/MS individuals, systolic blood pressure was lower by 15 mm Hg in ZZ homozygotes (n=6, P=0.03) and 9 mm Hg in MZ heterozygotes with IHD (n=39, P=0.02). Odds ratios for ICVD and IHD in MZ versus MM/MS individuals were 0.70 (0.51 to 0.96) and 0.77 (0.61 to 0.98). Finally, mean ages of MZ and MM/MS control subjects were 58 and 56 years (Mann-Whitney: P=0.008), and relative alpha(1)-antitrypsin MZ genotype frequencies increased from 20 to 93 years among control subjects (chi(2), P=0.002). CONCLUSIONS: ZZ alpha(1)-antitrypsin deficiency and MZ intermediate deficiency in the context of IHD are associated with reduced blood pressure, and MZ is associated with reduced risk of ICVD and IHD. Because MZ heterozygosity was associated with increased age, MZ heterozygosity could be a beneficial condition.
Notes
Comment In: Circulation. 2003 Aug 26;108(8):e62-3; author reply e62-312939251
PubMed ID
12578879 View in PubMed
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Body Mass Index and Risk of Alzheimer's Disease: A Mendelian Randomization Study of 399,536 Individuals.

https://arctichealth.org/en/permalink/ahliterature285946
Source
J Clin Endocrinol Metab. 2017 Jul 01;102(7):2310-2320
Publication Type
Article
Date
Jul-01-2017
Author
Liv Tybjærg Nordestgaard
Anne Tybjærg-Hansen
Børge G Nordestgaard
Ruth Frikke-Schmidt
Source
J Clin Endocrinol Metab. 2017 Jul 01;102(7):2310-2320
Date
Jul-01-2017
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Alzheimer Disease - epidemiology - etiology - genetics
Anthropometry - methods
Body mass index
Confounding Factors (Epidemiology)
Denmark - epidemiology
Female
Genotype
Humans
Male
Mendelian Randomization Analysis
Middle Aged
Risk factors
Thinness - complications - epidemiology - genetics
Young Adult
Abstract
Recently, data on 2,000,000 people established that low body mass index (BMI) is associated with increased risk of dementia. Whether this observational association reflects a causal effect remains to be clarified.
We tested the hypothesis that there is a causal association between low BMI and high risk of Alzheimer's disease.
Using a Mendelian randomization approach, we studied 95,578 individuals from the Copenhagen General Population Study (CGPS) with up to 36 years of follow-up and consortia data on 303,958 individuals from the Genetic Investigation of Anthropometric Traits (GIANT) and the International Genomics of Alzheimer's Project (IGAP).
Risk of Alzheimer's disease.
The causal odds ratio for a 1-kg/m2 genetically determined lower BMI was 0.98 [95% confidence interval (CI), 0.77 to 1.23] for a weighted allele score in the CGPS. Using 32 BMI-decreasing variants from GIANT and IGAP the causal odds ratio for Alzheimer's disease for a 1-standard deviation (SD) lower genetically determined BMI was 1.02 (95% CI, 0.86 to 1.22). Corresponding observational hazard ratios from the CGPS were 1.07 (95% CI, 1.05 to 1.09) and 1.32 (95% CI, 1.20 to 1.46) for a 1-kg/m2 and a 1-SD lower BMI, respectively.
Genetic and hence lifelong low BMI is not associated with increased risk of Alzheimer's disease in the general population. These data suggest that low BMI is not a causal risk factor for Alzheimer's disease and that the corresponding observational association likely is explained by reverse causation or confounding.
Notes
Cites: Clin Chem. 1972 Jun;18(6):499-5024337382
Cites: Stat Med. 1989 May;8(5):551-612657958
Cites: BMJ. 2005 Jun 11;330(7504):136015863436
Cites: Hypertension. 2009 Jul;54(1):84-9019470880
Cites: Arch Neurol. 2009 Mar;66(3):336-4219273752
Cites: Diabetes. 2015 Sep;64(9):3328-3325972569
Cites: Arch Neurol. 2005 Oct;62(10):1556-6016216938
Cites: J Intern Med. 2007 Dec;262(6):643-5017986201
Cites: Dement Geriatr Cogn Disord. 2007;24(3):220-817690555
Cites: J Neurol Neurosurg Psychiatry. 2002 Oct;73(4):371-612235302
Cites: Eur J Epidemiol. 2015 Jul;30(7):543-5225773750
Cites: Alzheimers Dement. 2015 Dec;11(12 ):1439-145126079416
Cites: JAMA. 2008 Jun 4;299(21):2524-3218523221
Cites: Lancet Diabetes Endocrinol. 2015 Jun;3(6):431-43625866264
Cites: Nat Genet. 2010 Nov;42(11):937-4820935630
Cites: Eur Neuropsychopharmacol. 2014 Dec;24(12):1982-9924704273
Cites: J Am Geriatr Soc. 2008 Dec;56(12):2261-619093925
Cites: N Engl J Med. 2014 Jul 3;371(1):32-4124941082
Cites: Obesity (Silver Spring). 2013 Jan;21(1):E51-523401370
Cites: Neuroimage. 2006 Jul 15;31(4):1419-2516545583
Cites: J Alzheimers Dis. 2015;43(3):739-5525147111
Cites: Nat Genet. 2009 Oct;41(10):1094-919734903
Cites: Int J Obes (Lond). 2008 Sep;32(9):1431-718607383
Cites: Nat Genet. 2013 Dec;45(12):1452-824162737
Cites: Alzheimers Dement. 2015 Dec;11(12 ):1430-143826079414
Cites: Stat Med. 2008 Apr 15;27(8):1133-6317886233
Cites: JAMA. 2010 May 12;303(18):1832-4020460622
Cites: Lancet. 2013 Apr 13;381(9874):1293-30123433573
Cites: Lancet. 2011 Feb 12;377(9765):557-6721295846
Cites: Neurology. 2008 Sep 30;71(14):1057-6418367704
Cites: Ann Neurol. 2015 Feb;77(2):301-1125469919
Cites: Neurology. 2004 Nov 23;63(10 ):1876-8115557505
Cites: PLoS Med. 2015 Jun 16;12(6):e1001841; discussion e100184126079503
Cites: Hum Mol Genet. 2014 Sep 15;23(R1):R89-9825064373
PubMed ID
28609829 View in PubMed
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Change in Body Mass Index Associated With Lowest Mortality in Denmark, 1976-2013.

https://arctichealth.org/en/permalink/ahliterature272857
Source
JAMA. 2016 May 10;315(18):1989-96
Publication Type
Article
Date
May-10-2016
Author
Shoaib Afzal
Anne Tybjærg-Hansen
Gorm B Jensen
Børge G Nordestgaard
Source
JAMA. 2016 May 10;315(18):1989-96
Date
May-10-2016
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Body Height
Body mass index
Body Weight
Cardiovascular Diseases - mortality
Cause of Death - trends
Cohort Studies
Denmark
Female
Humans
Male
Middle Aged
Neoplasms - mortality
Proportional Hazards Models
Abstract
Research has shown a U-shaped pattern in the association of body mass index (BMI) with mortality. Although average BMI has increased over time in most countries, the prevalence of cardiovascular risk factors may also be decreasing among obese individuals over time. Thus, the BMI associated with lowest all-cause mortality may have changed.
To determine whether the BMI value that is associated with the lowest all-cause mortality has increased in the general population over a period of 3 decades.
Three cohorts from the same general population enrolled at different times: the Copenhagen City Heart Study in 1976-1978 (n?=?13,704) and 1991-1994 (n?=?9482) and the Copenhagen General Population Study in 2003-2013 (n?=?97,362). All participants were followed up from inclusion in the studies to November 2014, emigration, or death, whichever came first.
For observational studies, BMI was modeled using splines and in categories defined by the World Health Organization. Body mass index was calculated as weight in kilograms divided by height in meters squared.
Main outcome was all-cause mortality and secondary outcomes were cause-specific mortality.
The number of deaths during follow-up was 10,624 in the 1976-1978 cohort (78% cumulative mortality; mortality rate [MR], 30/1000 person-years [95%CI, 20-46]), 5025 in the 1991-1994 cohort (53%; MR, 16/1000 person-years [95%CI, 9-30]), and 5580 in the 2003-2013 cohort (6%;MR, 4/1000 person-years [95%CI, 1-10]). Except for cancer mortality, the association of BMI with all-cause, cardiovascular, and other mortality was curvilinear (U-shaped). The BMI associated with the lowest all-cause mortality increased by 3.3 from the 1976-1978 cohort compared with the 2003-2013 cohort. [table: see text] The multivariable-adjusted hazard ratios for all-cause mortality for BMI of 30 or more vs BMI of 18.5 to 24.9 were 1.31 (95%CI, 1.23-1.39;MR, 46/1000 person-years [95%CI, 32-66] vs 28/1000 person-years [95%CI, 18-45]) in the 1976-1978 cohort, 1.13 (95%CI, 1.04-1.22; MR, 28/1000 person-years [95%CI, 17-47] vs 15/1000 person-years [95%CI, 7-31]) in the 1991-1994 cohort, and 0.99 (95%CI, 0.92-1.07;MR, 5/1000 person-years [95%CI, 2-12] vs 4/1000 person-years [95%CI, 1-11]) in the 2003-2013 cohort. CONCLUSIONS AND RELEVANCE Among 3 Danish cohorts, the BMI associated with the lowest all-cause mortality increased by 3.3 from cohorts enrolled from 1976-1978 through 2003-2013. Further investigation is needed to understand the reason for this change and its implications.
PubMed ID
27163987 View in PubMed
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