期刊
HYPERTENSION
卷 57, 期 5, 页码 903-U99出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.110.158667
关键词
drug target; genome-wide; SNP; hypertension; blood pressure
资金
- National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652]
- National Institute of Neurological Disorders and Stroke
- National Center for Research Resources [M01-RR00425]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]
- Affymetrix, Inc [N02-HL-6-4278]
- Robert Dawson Evans Endowment of the Boston University School of Medicine Department of Medicine
- Boston Medical Center
- Erasmus Medical Center and Erasmus University Rotterdam
- Netherlands Organization for Scientific Research
- Netherlands Organization for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly
- Netherlands Heart Foundation
- Ministry of Education, Culture, and Science
- the Ministry of Health, Welfare, and Sports
- European Commission
- Municipality of Rotterdam
- Netherlands Organization for Scientific Research (NWO Groot) [175.010.2005.011, 911.03.012]
- Research Institute for Diseases in the Elderly [014.93.015, RIDE2]
- Netherlands Genomics Initiative/Netherlands Organization for Scientific Research [050-060-810]
- National Genomics Initiative Centre for Medical Systems Biology
- Netherlands Centre for Healthy Aging
- Doris Duke Charitable Foundation
- Burroughs Wellcome Fund
- National Institutes of Health [N01-AG-12100, HHSN268200625226C]
- National Institute on Aging Intramural Research, Hjartavernd
- National Human Genome Research Institute [U01HG004402]
- National Institute for Health Research Biomedical Research Unit
- National Heart, Lung, and Blood Institute. [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022, R01HL087641, R01HL59367, R37HL051021, R01HL086694, U10HL054512]
- [UL1RR025005]
- Medical Research Council [G9521010] Funding Source: researchfish
- MRC [G9521010] Funding Source: UKRI
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 (beta : 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P = 4.7 x 10(-10)), diastolic blood pressure (beta : 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P = 9.5 x 10(-10)), and prevalence of hypertension (beta : 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P = 3.3 x 10(-4)). Variation in AGT (rs2004776) was associated with systolic blood pressure (beta : 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P = 3.8 x 10(-6)), as well as diastolic blood pressure (P = 5.0 x 10(-8)) and hypertension (P = 3.7 x 10(-7)). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (beta : 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P = 3.0 x 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. (Hypertension. 2011;57:903-910.) . Online Data Supplement
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