Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure

被引：339

作者：

Newton-Cheh, Christopher ^{[1
,2
,3
,4
]}

Larson, Martin G. ^{[4
,5
]}

Vasan, Ramachandran S. ^{[4
,6
,7
]}

Levy, Daniel ^{[4
,8
]}

Bloch, Kenneth D. ^{[2
,9
]}

Surti, Aarti ^{[3
]}

Guiducci, Candace ^{[3
]}

Kathiresan, Sekar ^{[1
,2
,3
,4
]}

Benjamin, Emelia J. ^{[4
,6
,7
]}

Struck, Joachim ^{[10
]}

Morgenthaler, Nils G. ^{[10
]}

Bergmann, Andreas ^{[10
]}

Blankenberg, Stefan ^{[11
]}

Kee, Frank ^{[12
]}

Nilsson, Peter ^{[13
]}

Yin, Xiaoyan ^{[4
]}

Peltonen, Leena ^{[14
,15
,16
]}

Vartiainen, Erkki ^{[14
]}

Salomaa, Veikko ^{[14
]}

Hirschhorn, Joel N. ^{[3
,17
,18
,19
]}

Melander, Olle ^{[13
]}

Wang, Thomas J. ^{[2
,4
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA

[3] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA

[4] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[5] Boston Univ, Sch Med, Dept Math, Boston, MA 02215 USA

[6] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA

[7] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA

[8] NHLBI, Bethesda, MD 20892 USA

[9] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA

[10] BRAHMS AG, Dept Res, D-16761 Hennigsdorf, Germany

[11] Johannes Gutenberg Univ Mainz, Dept Med 2, D-55131 Mainz, Germany

[12] Royal Victoria Hosp, Ctr Excellence Publ Hlth NI, A UKCRC, Belfast BT12 6BJ, Antrim, North Ireland

[13] Malmo Univ Hosp, CRC, SE-20502 Malmo, Sweden

[14] KTL Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FI-00300 Helsinki, Finland

[15] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[16] Inst Mol Med Finland FIMM, Biomedicum Helsinki, FI-00290 Helsinki, Finland

[17] Childrens Hosp, Program Genom, Boston, MA 02115 USA

[18] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[19] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 03期

关键词：

CARDIOVASCULAR-DISEASE; RISK; IMPACT; HYPERTENSION; CONTRIBUTE; MUTATIONS; MORTALITY; FINLAND; PROJECT; LINKAGE;

D O I：

10.1038/ng.328

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.

引用

页码：348 / 353

页数：6

共 30 条

[21] Regulatable atrial natriuretic peptide gene therapy for hypertension [J].

Schillinger, KJ ;

Tsai, SY ;

Taffet, GE ;

Reddy, AK ;

Marian, AJ ;

Entman, ML ;

Oka, K ;

Chan, L ;

O'Malley, BW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :13789-13794

[22] Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies [J].

Skol, AD ;

Scott, LJ ;

Abecasis, GR ;

Boehnke, M .

NATURE GENETICS, 2006, 38 (02) :209-213

[23] 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? [J].

Smith, GD ;

Ebrahim, S .

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2003, 32 (01) :1-22

[24] Cardiovascular risk factor changes in Finland, 1972-1997 [J].

Vartiainen, E ;

Jousilahti, P ;

Alfthan, G ;

Sundvall, J ;

Pietinen, P ;

Puska, P .

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2000, 29 (01) :49-56

[25] Impact of high-normal blood pressure on the risk of cardiovascular disease. [J].

Vasan, RS ;

Larson, MG ;

Leip, EP ;

Evans, JC ;

O'Donnell, CJ ;

Kannel, WB ;

Levy, D .

NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (18) :1291-1297

[26] Genetic variance of SGK-1 is associated with blood pressure, blood pressure change over time and strength of the insulin-diastolic blood pressure relationship [J].

von Wowern, F ;

Berglund, G ;

Carlson, J ;

Månsson, H ;

Hedblad, B ;

Melander, O .

KIDNEY INTERNATIONAL, 2005, 68 (05) :2164-2172

[27] Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals [J].

Wang, Thomas J. ;

Larson, Martin G. ;

Keyes, Michelle J. ;

Levy, Daniel ;

Benjamin, Emelia J. ;

Vasan, Ramachandran S. .

CIRCULATION, 2007, 115 (11) :1345-1353

[28] Impact of obesity on plasma natriuretic peptide levels [J].

Wang, TJ ;

Larson, MG ;

Levy, D ;

Benjamin, EJ ;

Leip, EP ;

Wilson, PWF ;

Vasan, RS .

CIRCULATION, 2004, 109 (05) :594-600

[29] Heritability and genetic linkage of plasma natriuretic peptide levels [J].

Wang, TJ ;

Larson, MG ;

Levy, D ;

Benjamin, EJ ;

Corey, D ;

Leip, EP ;

Vasan, RS .

CIRCULATION, 2003, 108 (01) :13-16

[30] Impact of age and sex on plasma natriuretic peptide levels in healthy adults [J].

Wang, TJ ;

Larson, MG ;

Levy, D ;

Leip, EP ;

Benjamin, EJ ;

Wilson, PWF ;

Sutherland, P ;

Omland, T ;

Vasan, RS .

AMERICAN JOURNAL OF CARDIOLOGY, 2002, 90 (03) :254-258

← 1 2 3 →