Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients

BACKGROUND: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. METHODS: To study genetic variation affecting BP dipping, we conducted a GWAS in Geneti...

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Autores principales: Rimpelä, Jenni M., Pörsti, Ilkka H., Jula, Antti, Lehtimäki, Terho, Niiranen, Teemu J., Oikarinen, Lasse, Porthan, Kimmo, Tikkakoski, Antti, Virolainen, Juha, Kontula, Kimmo K., Hiltunen, Timo P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032801/
https://www.ncbi.nlm.nih.gov/pubmed/29973135
http://dx.doi.org/10.1186/s12881-018-0624-7
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author Rimpelä, Jenni M.
Pörsti, Ilkka H.
Jula, Antti
Lehtimäki, Terho
Niiranen, Teemu J.
Oikarinen, Lasse
Porthan, Kimmo
Tikkakoski, Antti
Virolainen, Juha
Kontula, Kimmo K.
Hiltunen, Timo P.
author_facet Rimpelä, Jenni M.
Pörsti, Ilkka H.
Jula, Antti
Lehtimäki, Terho
Niiranen, Teemu J.
Oikarinen, Lasse
Porthan, Kimmo
Tikkakoski, Antti
Virolainen, Juha
Kontula, Kimmo K.
Hiltunen, Timo P.
author_sort Rimpelä, Jenni M.
collection PubMed
description BACKGROUND: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. METHODS: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P < 1 × 10(− 5) were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES. RESULTS: In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (β = − 4.8%, P = 9.6 × 10(− 9) for systolic and β = − 4.3%, P = 2.2 × 10(− 6) for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 × 10(− 5). The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (β = − 0.8%, P = 0.4 for systolic and β = − 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (β = − 7.6 g/m(2), P = 0.02). CONCLUSIONS: rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0624-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-60328012018-07-11 Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients Rimpelä, Jenni M. Pörsti, Ilkka H. Jula, Antti Lehtimäki, Terho Niiranen, Teemu J. Oikarinen, Lasse Porthan, Kimmo Tikkakoski, Antti Virolainen, Juha Kontula, Kimmo K. Hiltunen, Timo P. BMC Med Genet Research Article BACKGROUND: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. METHODS: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P < 1 × 10(− 5) were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES. RESULTS: In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (β = − 4.8%, P = 9.6 × 10(− 9) for systolic and β = − 4.3%, P = 2.2 × 10(− 6) for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 × 10(− 5). The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (β = − 0.8%, P = 0.4 for systolic and β = − 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (β = − 7.6 g/m(2), P = 0.02). CONCLUSIONS: rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0624-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-04 /pmc/articles/PMC6032801/ /pubmed/29973135 http://dx.doi.org/10.1186/s12881-018-0624-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Rimpelä, Jenni M.
Pörsti, Ilkka H.
Jula, Antti
Lehtimäki, Terho
Niiranen, Teemu J.
Oikarinen, Lasse
Porthan, Kimmo
Tikkakoski, Antti
Virolainen, Juha
Kontula, Kimmo K.
Hiltunen, Timo P.
Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients
title Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients
title_full Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients
title_fullStr Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients
title_full_unstemmed Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients
title_short Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients
title_sort genome-wide association study of nocturnal blood pressure dipping in hypertensive patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032801/
https://www.ncbi.nlm.nih.gov/pubmed/29973135
http://dx.doi.org/10.1186/s12881-018-0624-7
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