Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population
AU - Tobin, Martin D.
AU - Tomaszewski, Maciej
AU - Braund, Peter S.
AU - Hajat, Cother
AU - Raleigh, Stuart M.
AU - Palmer, Thomas M.
AU - Caulfield, Mark
AU - Burton, Paul R.
AU - Samani, Nilesh J.
PY - 2008/6
Y1 - 2008/6
N2 - The genes responsible for several monogenic hypertensive and hypotensive disorders have been identified. Our aim was to evaluate whether common variants in these genes affect blood pressure in the general population. We studied 2037 adults from 520 nuclear families characterized for 24-hour ambulatory blood pressure and related cardiovascular traits. We genotyped 298 tagging and putative functional single nucleotide polymorphisms, achieving a median coverage of 82.4% across 11 candidate loci. Five polymorphisms in the KCNJ1 gene coding for the potassium channel, ROMK, showed associations with mean 24-hour systolic or diastolic blood pressure. The strongest association was with an intronic polymorphism, rs2846679, where the minor allele (frequency 16%) was associated with a -1.58 (95% CI -2.47 to -0.69) mm Hg change in mean 24-hour systolic blood pressure, after accounting for age, sex, and familial correlations (P=0.00048). Polymorphisms in the gene were also associated with clinic blood pressure and left ventricular mass as assessed by ECG Sokolow-Lyon voltage (P=0.0081 for rs675759). Associations with mean 24-hour systolic or diastolic blood pressure were also observed for variants in CASR, NR3C2, SCNN1B, and SCNN1G. The findings show that common variants in genes responsible for some Mendelian disorders of hypertension and hypotension affect blood pressure in the general population. Notably, variants in KCNJ1, which causes Bartter syndrome type 2, were strongly associated, potentially providing a novel target for intervention.
AB - The genes responsible for several monogenic hypertensive and hypotensive disorders have been identified. Our aim was to evaluate whether common variants in these genes affect blood pressure in the general population. We studied 2037 adults from 520 nuclear families characterized for 24-hour ambulatory blood pressure and related cardiovascular traits. We genotyped 298 tagging and putative functional single nucleotide polymorphisms, achieving a median coverage of 82.4% across 11 candidate loci. Five polymorphisms in the KCNJ1 gene coding for the potassium channel, ROMK, showed associations with mean 24-hour systolic or diastolic blood pressure. The strongest association was with an intronic polymorphism, rs2846679, where the minor allele (frequency 16%) was associated with a -1.58 (95% CI -2.47 to -0.69) mm Hg change in mean 24-hour systolic blood pressure, after accounting for age, sex, and familial correlations (P=0.00048). Polymorphisms in the gene were also associated with clinic blood pressure and left ventricular mass as assessed by ECG Sokolow-Lyon voltage (P=0.0081 for rs675759). Associations with mean 24-hour systolic or diastolic blood pressure were also observed for variants in CASR, NR3C2, SCNN1B, and SCNN1G. The findings show that common variants in genes responsible for some Mendelian disorders of hypertension and hypotension affect blood pressure in the general population. Notably, variants in KCNJ1, which causes Bartter syndrome type 2, were strongly associated, potentially providing a novel target for intervention.
KW - Adolescent
KW - Adult
KW - Blood Pressure
KW - Epithelial Sodium Channels
KW - Family Health
KW - Female
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Genotype
KW - Humans
KW - Hypertension
KW - Hypotension
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Potassium Channels, Inwardly Rectifying
KW - Receptors, Calcium-Sensing
KW - Receptors, Mineralocorticoid
KW - Risk Factors
U2 - 10.1161/HYPERTENSIONAHA.108.112664
DO - 10.1161/HYPERTENSIONAHA.108.112664
M3 - Journal article
C2 - 18443236
VL - 51
SP - 1658
EP - 1664
JO - Hypertension
JF - Hypertension
SN - 1524-4563
IS - 6
ER -