Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population. Physiol Genomics 2013 Feb 15;45(4):138-50
Date
12/28/2012Pubmed ID
23269701Pubmed Central ID
PMC3774577DOI
10.1152/physiolgenomics.00037.2012Scopus ID
2-s2.0-84874062990 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation.
Author List
Arenas IA, Tremblay J, Deslauriers B, Sandoval J, Ĺ eda O, Gaudet D, Merlo E, Kotchen T, Cowley AW Jr, Hamet PAuthor
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptation, PhysiologicalAdult
Algorithms
Blood Pressure
Family Health
Female
Founder Effect
Genetic Linkage
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Hypertension
Male
Models, Genetic
Phenotype
Polymorphism, Single Nucleotide
Posture
Siblings
Supine Position