A Population Association Study of Angiotensinogen Polymorphisms and Haplotypes With Left Ventricular Phenotypes

Several studies have shown an association between single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene and hypertension. Because hypertension is a risk factor for left ventricular (LV) hypertrophy and because evidence from animal models suggests that AGT may play a role in the growth and hypertrophy of the heart, we chose to conduct a population association study examining the relationship of 10 SNPs in the AGT gene with 7 different LV phenotypes measured by echocardiography. Participants (336 whites and 441 blacks) were drawn from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Individuals were genotyped for 10 previously identified SNPs within the AGT gene. SNP genotype results were regressed against continuous LV phenotypes to test associations separately in each race. Using a cutoff of P<0.005 to account for multiple testing, we found 1 SNP (rs943580) significantly associated with transmitral early peak filling velocity (MVE) in the black population. We also used Phase 2.0.2 to reconstruct haplotypes from genotype data. Using the same cutoff of P<0.005, we found no haplotypes to be significantly associated with the LV phenotypes. To better understand the association between rs943580 and MVE, we examined AGT haplotype associations with MVE. The single SNP association was driven by a large group of SNPs in high linkage disequilibrium that includes the promoter SNP rs5051.

[1]  A. Chakravarti,et al.  Haplotype Association Analysis of AGT Variants with Hypertension-Related Traits: The HyperGEN Study , 2005, Human Heredity.

[2]  N. Saitou,et al.  Natural selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world. , 2004, American journal of human genetics.

[3]  Peter Donnelly,et al.  A comparison of bayesian methods for haplotype reconstruction from population genotype data. , 2003, American journal of human genetics.

[4]  M. Rieder,et al.  An association study of angiotensinogen polymorphisms with serum level and hypertension in an African-American population , 2003, Journal of hypertension.

[5]  A. Chakravarti,et al.  Linkage disequilibrium and haplotype diversity in the genes of the renin-angiotensin system: findings from the family blood pressure program. , 2003, Genome research.

[6]  H. Melhus,et al.  Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial , 2002, Journal of hypertension.

[7]  Yuling Hong,et al.  Sibling correlation of left ventricular mass and geometry in hypertensive African Americans and whites: the HyperGEN study. Hypertension Genetic Epidemiology Network. , 2001, American journal of hypertension.

[8]  R. Devereux,et al.  Relationship Between Left Ventricular Diastolic Relaxation and Systolic Function in Hypertension: The Hypertension Genetic Epidemiology Network (HyperGEN) Study , 2001, Hypertension.

[9]  P. Donnelly,et al.  A new statistical method for haplotype reconstruction from population data. , 2001, American journal of human genetics.

[10]  R. Devereux,et al.  Effect of Type 2 Diabetes Mellitus on Left Ventricular Geometry and Systolic Function in Hypertensive Subjects: Hypertension Genetic Epidemiology Network (HyperGEN) Study , 2001, Circulation.

[11]  T. Ogihara,et al.  Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension. , 2000, Life sciences.

[12]  M A Province,et al.  NHLBI family blood pressure program: methodology and recruitment in the HyperGEN network. Hypertension genetic epidemiology network. , 2000, Annals of epidemiology.

[13]  R. Devereux,et al.  Reliability of echocardiographic assessment of left ventricular structure and function: the PRESERVE study. Prospective Randomized Study Evaluating Regression of Ventricular Enlargement. , 1999, Journal of the American College of Cardiology.

[14]  C. Lau,et al.  Relations of diastolic left ventricular filling to systolic chamber and myocardial contractility in hypertensive patients with left ventricular hypertrophy (The PRESERVE Study). , 1999, The American journal of cardiology.

[15]  J. Karjalainen,et al.  Angiotensinogen gene M235T polymorphism predicts left ventricular hypertrophy in endurance athletes. , 1999, Journal of the American College of Cardiology.

[16]  J. Jeng.  Left ventricular mass, carotid wall thickness, and angiotensinogen gene polymorphism in patients with hypertension. , 1999, American journal of hypertension.

[17]  P. Kwok,et al.  Fluorescence polarization in homogeneous nucleic acid analysis. , 1999, Genome research.

[18]  R. Cooper,et al.  Influence of left ventricular geometric patterns on prognosis in patients with or without coronary artery disease. , 1998, Journal of the American College of Cardiology.

[19]  M Yamada,et al.  Homogeneity of kerato-epithelin codon 124 mutations in Japanese patients with either of two types of corneal stromal dystrophy. , 1997, American journal of human genetics.

[20]  D. Levy,et al.  Heritability of left ventricular mass: the Framingham Heart Study. , 1997, Hypertension.

[21]  J. Lalouel,et al.  Haplotypes of angiotensinogen in essential hypertension. , 1997, American journal of human genetics.

[22]  John Quackenbush,et al.  A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. , 1997, The Journal of clinical investigation.

[23]  J. Gardin,et al.  Relationship of cardiovascular risk factors to echocardiographic left ventricular mass in healthy young black and white adult men and women. The CARDIA study. Coronary Artery Risk Development in Young Adults. , 1995, Circulation.

[24]  N. Iwai,et al.  Angiotensinogen gene and blood pressure in the Japanese population. , 1995, Hypertension.

[25]  A. Folsom,et al.  Black-white differences in electrocardiographic left ventricular mass and its association with blood pressure (the ARIC study) , 1994 .

[26]  A. Folsom,et al.  Black-white differences in electrocardiographic left ventricular mass and its association with blood pressure (the ARIC study). Atherosclerosis Risk in Communities. , 1994, The American journal of cardiology.

[27]  J. Laragh,et al.  Comparison of left ventricular mass and geometry in black and white patients with essential hypertension. , 1993, American journal of hypertension.

[28]  H. Jacob,et al.  Vascular Injury Induces Angiotensinogen Gene Expression in the Media and Neointima , 1993, Circulation.

[29]  R. Devereux,et al.  Two-dimensional echocardiographic aortic root dimensions in normal children and adults. , 1989, The American journal of cardiology.

[30]  N. Reichek,et al.  Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. , 1989, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[31]  A. DeMaria,et al.  Recommendations Regarding Quantitation in M-Mode Echocardiography: Results of a Survey of Echocardiographic Measurements , 1978, Circulation.