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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
Vimaleswaran, Karani S; Cavadino, Alana; Berry, Diane J; Jorde, Rolf; Dieffenbach, Aida Karina; Lu, Chen; Alves, Alexessander Couto; Heerspink, Hiddo J Lambers; Tikkanen, Emmi; Eriksson, Joel; Wong, Andrew; Mangino, Massimo; Jablonski, Kathleen A; Nolte, Ilja M; Houston, Denise K; Ahluwalia, Tarunveer Singh; van der Most, Peter J; Pasko, Dorota; Zgaga, Lina; Thiering, Elisabeth; Vitart, Veronique; Fraser, Ross M; Huffman, Jennifer E; de Boer, Rudolf A; Schöttker, Ben; Saum, Kai-Uwe; McCarthy, Mark I; Dupuis, Josée; Herzig, Karl-Heinz; Sebert, Sylvain; Pouta, Anneli; Laitinen, Jaana; Kleber, Marcus E; Navis, Gerjan; Lorentzon, Mattias; Jameson, Karen; Arden, Nigel; Cooper, Jackie A; Acharya, Jayshree; Hardy, Rebecca; Raitakari, Olli; Ripatti, Samuli; Billings, Liana K; Lahti, Jari; Osmond, Clive; Penninx, Brenda W; Rejnmark, Lars; Lohman, Kurt K; Paternoster, Lavinia; Stolk, Ronald P.
Afiliação
  • Vimaleswaran KS; Population, Policy and Practice, UCL Institute of Child Health, London, UK; Hugh Sinclair Unit of Human Nutrition, Department of Food & Nutritional Sciences, School of Chemistry, Food & Pharmacy, University of Reading, Reading, UK.
  • Cavadino A; Population, Policy and Practice, UCL Institute of Child Health, London, UK.
  • Berry DJ; Population, Policy and Practice, UCL Institute of Child Health, London, UK.
  • Jorde R; Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
  • Dieffenbach AK; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
  • Lu C; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Alves AC; Department of Epidemiology and Biostatistics, Imperial College London, London, UK; Institute of Health Sciences, University of Oulu, Oulu, Finland.
  • Heerspink HJ; Department of Clinical Pharmacology, University Medical Center, University of Groningen, Groningen, Netherlands.
  • Tikkanen E; Institute for Molecular Medicine Finland, Tukholmankatu, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Hjelt Institute, University of Helsinki, Helsinki, Finland.
  • Eriksson J; Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Wong A; MRC Unit for Lifelong Health and Ageing, University College London, London, UK.
  • Mangino M; Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Campus, London, UK.
  • Jablonski KA; Biostatistics Center, Department of Epidemiology and Biostatistics, School of Public Health, George Washington University, Rockville, MD, USA.
  • Nolte IM; Department of Epidemiology, University Medical Center, University of Groningen, Groningen, Netherlands.
  • Houston DK; Gerontology and Geriatric Medicine, Department of Internal Medicine, and J Paul Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Ahluwalia TS; Metabolic Genetics, Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen,
  • van der Most PJ; Department of Epidemiology, University Medical Center, University of Groningen, Groningen, Netherlands.
  • Pasko D; Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.
  • Zgaga L; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK; Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
  • Thiering E; Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Division of Metabolic Diseases and Nutritional Medicine, Ludwig Maximilian University of Munich, Dr von Hauner Children's Hospital, Munich, Germany.
  • Vitart V; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Fraser RM; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
  • Huffman JE; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • de Boer RA; Department of Cardiology, University Medical Center, University of Groningen, Groningen, Netherlands.
  • Schöttker B; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
  • Saum KU; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
  • McCarthy MI; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, Oxford, UK.
  • Dupuis J; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
  • Herzig KH; Institute of Biomedicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland.
  • Sebert S; Biocenter Oulu, University of Oulu, Oulu, Finland; Institute of Health Sciences, University of Oulu, Oulu, Finland.
  • Pouta A; Obstetrics and Gynecology, Department of Clinical Sciences, Oulu University Hospital, Oulu, Finland; National Institute for Health and Welfare, Oulu, Finland.
  • Laitinen J; Finnish Institute of Occupational Health, Helsinki, Finland.
  • Kleber ME; Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
  • Navis G; Department of Internal Medicine, Division of Nephrology, University Medical Center, University of Groningen, Groningen, Netherlands.
  • Lorentzon M; Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Jameson K; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Arden N; NIHR Oxford Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Cooper JA; Cardiovascular Genetics, BHF Laboratories, Institute of Cardiovascular Science, University College London, London, UK.
  • Acharya J; Cardiovascular Genetics, BHF Laboratories, Institute of Cardiovascular Science, University College London, London, UK.
  • Hardy R; MRC Unit for Lifelong Health and Ageing, University College London, London, UK.
  • Raitakari O; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
  • Ripatti S; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Billings LK; Center for Human Genetic Research and Diabetes Research Center, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; NorthShore University HealthSystem, Evans
  • Lahti J; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
  • Osmond C; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Penninx BW; Department of Psychiatry, EMGO Institute, VU University Medical Centre, Amsterdam, Netherlands.
  • Rejnmark L; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Lohman KK; Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Paternoster L; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
  • Stolk RP; Department of Epidemiology, University Medical Center, University of Groningen, Groningen, Netherlands.
Lancet Diabetes Endocrinol ; 2(9): 719-29, 2014 Sep.
Article em En | MEDLINE | ID: mdl-24974252
ABSTRACT

BACKGROUND:

Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.

METHODS:

In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.

FINDINGS:

In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (ß per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (ß per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).

INTERPRETATION:

Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

FUNDING:

British Heart Foundation, UK Medical Research Council, and Academy of Finland.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vitamina D / Deficiência de Vitamina D / Polimorfismo de Nucleotídeo Único / Oxirredutases atuantes sobre Doadores de Grupo CH-CH / Colestanotriol 26-Mono-Oxigenase / Hipertensão Tipo de estudo: Clinical_trials / Etiology_studies / Risk_factors_studies / Systematic_reviews Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Lancet Diabetes Endocrinol Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vitamina D / Deficiência de Vitamina D / Polimorfismo de Nucleotídeo Único / Oxirredutases atuantes sobre Doadores de Grupo CH-CH / Colestanotriol 26-Mono-Oxigenase / Hipertensão Tipo de estudo: Clinical_trials / Etiology_studies / Risk_factors_studies / Systematic_reviews Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Lancet Diabetes Endocrinol Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Reino Unido