Recapitulation of two genomewide association studies on blood pressure and essential hypertension in the Korean population

Essential hypertension causes high rates of morbidity and mortality, primarily due to its complications, and its development is regulated by genetic risk and environmental factors. However, until recent genomewide association studies (GWASs) were reported, the genetic factors were unknown. Two GWASs on systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension in Caucasians—Global Blood Pressure Genetics (Global BPgen) and Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE)—reported 51 single-nucleotide polymorphisms (SNPs) in 12 loci at P<4 × 10−7. Because the prevalence, age of onset and severity of complications of hypertension vary between ethnic groups, we wanted to investigate these results in other ethnic groups. We examined the association of 27 of the 51 SNPs in 8512 unrelated individuals from Korean Association REsource (KARE), a GWAS that was based on epidemiological cohorts in Korea. Four loci—ATP2B1 (ATPase, Ca++ transporting, plasma membrane 1), CSK (c-src tyrosine kinase), CYP17A1 (cytochrome P450 17A1) and PLEKHA7 (pleckstrin homology domain-containing family A member 7)—were associated with blood pressure and hypertension in the Korean population.

[1]  Laurent Excoffier,et al.  Arlequin (version 3.0): An integrated software package for population genetics data analysis , 2005, Evolutionary bioinformatics online.

[2]  S WRIGHT,et al.  Genetical structure of populations. , 1950, Nature.

[3]  M. Waterman,et al.  Combined 17α-Hydroxylase/17,20-Lyase Deficiency due to a 7-Basepair Duplication in the N-Terminal Region of the Cytochrome P45017α (CYP17) Gene* , 1990 .

[4]  D. Levy,et al.  Isolated systolic hypertension: an important cardiovascular risk factor. , 1998, Blood pressure.

[5]  C. Barbagallo,et al.  Hypertension and diabetes mellitus are associated with cardiovascular events in the elderly without cardiovascular disease. Results of a 15-year follow-up in a Mediterranean population. , 2009, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[6]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[7]  Terence P. Speed,et al.  Genome analysis A genotype calling algorithm for affymetrix SNP arrays , 2005 .

[8]  Andrew D. Johnson,et al.  Genome-wide association study of blood pressure and hypertension , 2009, Nature Genetics.

[9]  J. Saavedra.  Studies on genes and hypertension: a daunting task , 2005, Journal of hypertension.

[10]  M. Takeichi,et al.  Anchorage of Microtubule Minus Ends to Adherens Junctions Regulates Epithelial Cell-Cell Contacts , 2008, Cell.

[11]  E. Schiffrin,et al.  Role of c-Src in the regulation of vascular contraction and Ca2+ signaling by angiotensin II in human vascular smooth muscle cells , 2001, Journal of hypertension.

[12]  W L Miller,et al.  Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[13]  I. Mungrue,et al.  Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle. , 2003, American journal of physiology. Cell physiology.

[14]  M. Hollenberg,et al.  cSrc is a major cytosolic tyrosine kinase in vascular tissue. , 1999, Canadian journal of physiology and pharmacology.

[15]  E. Schiffrin,et al.  Src Is an Important Mediator of Extracellular Signal–Regulated Kinase 1/2–Dependent Growth Signaling by Angiotensin II in Smooth Muscle Cells From Resistance Arteries of Hypertensive Patients , 2001, Hypertension.

[16]  I. Mungrue,et al.  Plasma Membrane Calcium ATPase Overexpression in Arterial Smooth Muscle Increases Vasomotor Responsiveness and Blood Pressure , 2003, Circulation research.

[17]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[18]  P. O’Reilly,et al.  Genome-wide association study identifies eight loci associated with blood pressure , 2009, Nature Genetics.

[19]  G. Martin.  The hunting of the Src , 2001, Nature Reviews Molecular Cell Biology.

[20]  S. Wright,et al.  Genetical Structure of Populations , 1950, Nature.

[21]  K. Kent,et al.  Activation of pp60c-src is necessary for human vascular smooth muscle cell migration. , 1997, Surgery.

[22]  Sangsoo Kim,et al.  A Scheme for Filtering SNPs Imputed in 8,842 Korean Individuals Based on the International HapMap Project Data , 2009 .

[23]  M. Waterman,et al.  Structural characterization of normal and mutant human steroid 17 alpha-hydroxylase genes: molecular basis of one example of combined 17 alpha-hydroxylase/17,20 lyase deficiency. , 1988, Molecular endocrinology.

[24]  E. Carafoli,et al.  The plasma membrane Ca2+ ATPase of animal cells: structure, function and regulation. , 2008, Archives of biochemistry and biophysics.

[25]  R. Auchus.  The genetics, pathophysiology, and management of human deficiencies of P450c17. , 2001, Endocrinology and metabolism clinics of North America.

[26]  M. Waterman,et al.  Structural Characterization of Normal and Mutant Human Steroid 17α- Hydroxylase Genes: Molecular Basis of One Example of Combined 17α- Hydroxylase/17,20 Lyase Deficiency , 1988 .

[27]  Taesung Park,et al.  A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits , 2009, Nature Genetics.