Multiple genes for essential-hypertension susceptibility on chromosome 1q.
Essential hypertension, defined as elevated levels of blood pressure (BP) without any obvious cause, is a major risk factor for coronary heart disease, stroke, and renal disease. BP levels and susceptibility to development of essential hypertension are partially determined by genetic factors that are poorly understood. Similar to other efforts to understand complex, non-Mendelian phenotypes, genetic dissection of hypertension-related traits employs genomewide linkage analyses of families and association studies of patient cohorts, to uncover rare and common disease alleles, respectively. Family-based mapping studies of elevated BP cover the large intermediate ground for identification of genes with common variants of significant effect. Our genomewide linkage and candidate-gene-based association studies demonstrate that a replicated linkage peak for BP regulation on human chromosome 1q, homologous to mouse and rat quantitative trait loci for BP, contains at least three genes associated with BP levels in multiple samples: ATP1B1, RGS5, and SELE. Individual variants in these three genes account for 2-5-mm Hg differences in mean systolic BP levels, and the cumulative effect reaches 8-10 mm Hg. Because the associated alleles in these genes are relatively common (frequency >5%), these three genes are important contributors to elevated BP in the population at large.
Chang
Yen-Pei Christy
YP
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Liu
Xin
X
Kim
James Dae Ok
JD
Ikeda
Morna A
MA
Layton
Marnie R
MR
Weder
Alan B
AB
Cooper
Richard S
RS
Kardia
Sharon L R
SL
Rao
D C
DC
Hunt
Steve C
SC
Luke
Amy
A
Boerwinkle
Eric
E
Chakravarti
Aravinda
A
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D019040:E-Selectin / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
C503551:ATP1B1 protein, human; D019040:E-Selectin; D020710:RGS Proteins; C491349:RGS5 protein, human; D000254:Sodium-Potassium-Exchanging ATPase