Vol. 60, No. 3, 2005
Issue release date: 2005
Hum Hered 2005;60:164–176
Original Paper
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Haplotype Association Analysis of AGT Variants with Hypertension-Related Traits: The HyperGEN Study

Gu C.C.a · Chang Y.-P.C.e · Hunt S.C.d · Schwander K.a · Arnett D.f · Djousse L.g · Heiss G.h · Oberman A.i · Lalouel J.-M.d · Province M.a, b · Chakravarti A.e · Rao D.C.a, b, c
aDivision of Biostatistics, and Departments of bGenetics and cPsychiatry, Washington University School of Medicine, St. Louis, Mo.; dUniversity of Utah School of Medicine, Salt Lake City, Utah; eInstitute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.; fUniversity of Minnesota and Department of Epidemiology, Minneapolis, Minn.; gEvans Department of Medicine, Section of Preventive Medicine & Epidemiology, Boston University, Boston, Mass.; hUniversity of North Carolina, Department of Epidemiology and UNC-CH School of Public Health, Chapel Hill, N.C.; iUAB, Division of Preventive Medicine, Birmingham, Ala., USA
email Corresponding Author

 goto top of outline Key Words

  • Hypertension
  • Intermediate phenotype
  • Blood pressure reactivity
  • BMI
  • Haplotype analysis
  • AGT
  • Genetic interaction

 goto top of outline Abstract

Objective: Function of the renin-angiotensin system is important to human hypertension, but its genetic etiology remains elusive. We set out to examine a hypothesis that multiple genetic variants in the system act together in blood pressure regulation, via intermediate phenotypes such as blood pressure reactivity. Methods: A sample of 531 hypertensive cases and 417 controls was selected from the HyperGEN study. Hypertension-related traits including blood pressure responses to challenges to math test, handgrip and postural change (mathBP, gripBP, and postBP), and body mass index (BMI) were analyzed for association with 10 single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene. Single-marker and haplotype analyses were performed to examine the effects of both individual and multiple variants. Multiple-trait profiling was used to assess interaction of latent intermediate factors with susceptible haplotypes. Results: In Blacks, two SNPs in exon 5 and 3′UTR showed significant association with gripBP, and two promoter SNPs were strongly associated with postBP. In Whites, only borderline association was found for 2 promoter SNPs with mathBP. Haplotype analyses in Blacks confirmed association with gripBP, and detected significant association of a haplotype to BMI (p =0.029). With the interactions modeled, haplotype associations found in Blacks remain significant, while significant associations to BMI (p = 0.009) and gripSBP emerged in Whites. Conclusion: Genetic variants in regulatory regions of AGT showed strong association with blood pressure reactivity. Interaction of promoter and genic SNPs in AGT revealed collective action of multiple variants on blood pressure reactivity and BMI both in Blacks and in Whites, possibly following different pathways.

Copyright © 2005 S. Karger AG, Basel

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 goto top of outline Author Contacts

Dr. C. Charles Gu
Division of Biostatistics, Washington University School of Medicine
Campus Box 8067, 660 S. Euclid Avenue
St. Louis, MO 63110 (USA)
Tel. +1 314 362 3642, Fax +1 314 362 2693, E-Mail gc@wubios.wustl.edu

 goto top of outline Article Information

Received: February 14, 2005
Accepted: September 19, 2005
Published online: December 12, 2005
Number of Print Pages : 13
Number of Figures : 5, Number of Tables : 5, Number of References : 56

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 60, No. 3, Year 2005 (Cover Date: 2005)

Journal Editor: Devoto, M. (Wilmington, Del.)
ISSN: 0001–5652 (print), 1423–0062 (Online)

For additional information: http://www.karger.com/HHE

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