Further evidence of a quantitative trait locus on chromosome 18 influencing postural change in systolic blood pressure: The hypertension genetic epidemiology network (HyperGEN) study

James S. Pankow, Diane M. Dunn, Steven Hunt, Mark F. Leppert, Michael B. Miller, D. C. Rao, Gerardo Heiss, Albert Oberman, Jean Marc Lalouel, Robert B. Weiss

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Postural change in systolic blood pressure (SBP) is prospectively associated with several disease outcomes including hypertension, stroke, and coronary heart disease. The objective of this study was to characterize further a possible quantitative trait locus on chromosome 18q21 influencing SBP response to a postural challenge. Methods: A prior genome scan of postural SBP response in 636 subjects of white ethnicity from 285 hypertensive sibships in the Hypertension Genetic Epidemiology Network (HyperGEN) indicated suggestive evidence for linkage on chromosome 18q21. This study included a de novo set of 452 African American pedigrees from the HyperGEN study and an expanded set of 372 white pedigrees. Variance components linkage analysis of postural SBP change was conducted using microsatellite markers on chromosome 18, and association studies were performed with a common single nucleotide polymorphism (variant 13) in the gene encoding NEDD4L, a key regulator of fine sodium reabsorption in the distal nephron. Results: Combined analysis of all white and African American pedigrees yielded a LOD score of 4.25 at 80 cM on chromosome 18q21, with at least nominal evidence of linkage at this position in both white (LOD: 3.43) and African American (LOD: 1.14) subjects. Postural SBP response was associated with variant 13 of the NEDD4L in a subset of white subjects taking medications effective in treating sodium volume-dependent hypertension (α1-blockers, calcium channel blockers, and/or diuretics). Conclusion: These data provide further evidence for a quantitative trait locus on chromosome 18q21 influencing postural change in SBP.

Original languageEnglish
Pages (from-to)672-678
Number of pages7
JournalAmerican Journal of Hypertension
Volume18
Issue number5
DOIs
Publication statusPublished - May 2005
Externally publishedYes

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Chromosomes, Human, Pair 18
Molecular Epidemiology
Quantitative Trait Loci
Blood Pressure
Hypertension
Pedigree
Chromosomes
African Americans
Sodium
Nephrons
Calcium Channel Blockers
Diuretics
Microsatellite Repeats
Single Nucleotide Polymorphism
Coronary Disease

Keywords

  • Antihypertensive agents
  • Blood pressure
  • Genetics
  • Polymorphism
  • Sodium channels

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Further evidence of a quantitative trait locus on chromosome 18 influencing postural change in systolic blood pressure : The hypertension genetic epidemiology network (HyperGEN) study. / Pankow, James S.; Dunn, Diane M.; Hunt, Steven; Leppert, Mark F.; Miller, Michael B.; Rao, D. C.; Heiss, Gerardo; Oberman, Albert; Lalouel, Jean Marc; Weiss, Robert B.

In: American Journal of Hypertension, Vol. 18, No. 5, 05.2005, p. 672-678.

Research output: Contribution to journalArticle

Pankow, James S. ; Dunn, Diane M. ; Hunt, Steven ; Leppert, Mark F. ; Miller, Michael B. ; Rao, D. C. ; Heiss, Gerardo ; Oberman, Albert ; Lalouel, Jean Marc ; Weiss, Robert B. / Further evidence of a quantitative trait locus on chromosome 18 influencing postural change in systolic blood pressure : The hypertension genetic epidemiology network (HyperGEN) study. In: American Journal of Hypertension. 2005 ; Vol. 18, No. 5. pp. 672-678.
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abstract = "Background: Postural change in systolic blood pressure (SBP) is prospectively associated with several disease outcomes including hypertension, stroke, and coronary heart disease. The objective of this study was to characterize further a possible quantitative trait locus on chromosome 18q21 influencing SBP response to a postural challenge. Methods: A prior genome scan of postural SBP response in 636 subjects of white ethnicity from 285 hypertensive sibships in the Hypertension Genetic Epidemiology Network (HyperGEN) indicated suggestive evidence for linkage on chromosome 18q21. This study included a de novo set of 452 African American pedigrees from the HyperGEN study and an expanded set of 372 white pedigrees. Variance components linkage analysis of postural SBP change was conducted using microsatellite markers on chromosome 18, and association studies were performed with a common single nucleotide polymorphism (variant 13) in the gene encoding NEDD4L, a key regulator of fine sodium reabsorption in the distal nephron. Results: Combined analysis of all white and African American pedigrees yielded a LOD score of 4.25 at 80 cM on chromosome 18q21, with at least nominal evidence of linkage at this position in both white (LOD: 3.43) and African American (LOD: 1.14) subjects. Postural SBP response was associated with variant 13 of the NEDD4L in a subset of white subjects taking medications effective in treating sodium volume-dependent hypertension (α1-blockers, calcium channel blockers, and/or diuretics). Conclusion: These data provide further evidence for a quantitative trait locus on chromosome 18q21 influencing postural change in SBP.",
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