Association of Hypertension Drug Target Genes With Blood Pressure and Hypertension in 86 588 Individuals
| العنوان: | Association of Hypertension Drug Target Genes With Blood Pressure and Hypertension in 86 588 Individuals |
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| المؤلفون: | Toby Johnson, Cornelia M. van Duijn, Aravinda Chakravarti, Kenneth Rice, Daniel Levy, Paul M. Ridker, Andrew D. Johnson, Germaine C. Verwoert, Vilmundur Gudnason, Lynda M. Rose, Christopher Newton-Cheh, Patricia B. Munroe, Mark J. Caulfield, Daniel I. Chasman, Martin G. Larson, Bruce M. Psaty, Lenore J. Launer, Georg Ehret |
| المساهمون: | Epidemiology |
| المصدر: | Hypertension, Vol. 57, No 5 (2011) pp. 903-10 Hypertension, 57(5), 903-U99. Lippincott Williams & Wilkins |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Genotype, medicine.drug_class, Angiotensinogen, Blood Pressure, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Receptors, Adrenergic, beta-1/genetics, Article, Polymorphism (computer science), Internal medicine, Internal Medicine, medicine, Humans, SNP, Genetic Predisposition to Disease, Allele, Antihypertensive drug, Antihypertensive Agents, Alleles, ddc:616, Genetics, business.industry, Antihypertensive Agents/pharmacology/therapeutic use, Blood Pressure/drug effects/genetics, Hypertension/drug therapy/genetics, Endocrinology, Blood pressure, Pharmacogenetics, Hypertension, Female, Receptors, Adrenergic, beta-1, Angiotensinogen/genetics, business |
| الوصف: | We previously conducted genome-wide association meta-analysis of systolic blood pressure, diastolic blood pressure, and hypertension in 29 136 people from 6 cohort studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Here we examine associations of these traits with 30 gene regions encoding known antihypertensive drug targets. We find nominal evidence of association of ADRB1 , ADRB2 , AGT , CACNA1A , CACNA1C , and SLC12A3 polymorphisms with 1 or more BP traits in the Cohorts for Heart and Aging Research in Genomic Epidemiology genome-wide association meta-analysis. We attempted replication of the top meta-analysis single nucleotide polymorphisms for these genes in the Global BPgen Consortium (n=34 433) and the Women's Genome Health Study (n=23 019) and found significant results for rs1801253 in ADRB1 (Arg389Gly), with the Gly allele associated with a lower mean systolic blood pressure (β: 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P= 4.7×10 −10 ), diastolic blood pressure (β: 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P= 9.5×10 −10 ), and prevalence of hypertension (β: 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P= 3.3×10 −4 ). Variation in AGT (rs2004776) was associated with systolic blood pressure (β: 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P= 3.8×10 −6 ), as well as diastolic blood pressure ( P= 5.0×10 −8 ) and hypertension ( P= 3.7×10 −7 ). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (β: 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P= 3.0×10 −5 ). Two loci, ADRB1 and AGT , contain single nucleotide polymorphisms that reached a genome-wide significance threshold in meta-analysis for the first time. Our findings suggest that these genes warrant further studies of their genetic effects on blood pressure, including pharmacogenetic interactions. |
| تدمد: | 1524-4563 0194-911X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::90eda3c34ac00df1acd9bc5b81c671adTest https://doi.org/10.1161/hypertensionaha.110.158667Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....90eda3c34ac00df1acd9bc5b81c671ad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244563 0194911X |
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