Further evidence of a quantitative trait locus on chromosome 18 influencing postural change in systolic blood pressure: the Hypertension Genetic Epidemiology Network (HyperGEN) Study.
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 (alpha1-blockers, calcium channel blockers, and/or diuretics).


CONCLUSIONS
These data provide further evidence for a quantitative trait locus on chromosome 18q21 influencing postural change in SBP.
Pankow
James S
JS
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota 55454, USA. pankow@epi.umn.edu
Dunn
Diane M
DM
Hunt
Steven C
SC
Leppert
Mark F
MF
Miller
Michael B
MB
Rao
D C
DC
Heiss
Gerardo
G
Oberman
Albert
A
Lalouel
Jean-Marc
JM
Weiss
Robert B
RB
D000328:Adult; D000368:Aged; D002887:Chromosomes, Human, Pair 18; D056827:Endosomal Sorting Complexes Required for Transport; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D000075702:Nedd4 Ubiquitin Protein Ligases; D011187:Posture; D040641:Quantitative Trait Loci; D013599:Systole; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases