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Genetic variants in the ADD1 and GNB3 genes and
blood pressure response to potassium supplementation |
Dai-Hai YU PhD1,Jian-Feng HUANG MD1,Ji-Chun CHEN MS1,Jie CAO MS1,Shu-Feng CHEN PhD1,Dong-Feng GU MD, PhD, for the GenSalt Collaborative Research Group1,De-Pei LIU PhD2,Lai-Yuan WANG PhD3,Jing CHEN MD, MSc4,Jiang HE MD, PhD4,Cashell E. JAQUISH PhD5,Dabeeru C. RAO PhD6,Charles GU PhD6,James E. HIXSON PhD7,Chung-Shiuan CHEN MS8,Paul K. WHELTON MD, MSc9, |
1.Department of Evidence-based
Medicine and Population Genetics, Cardiovascular Institute and Fu
Wai Hospital, Chinese Academy of Medical Sciences and Peking Union
Medical College, Beijing 100037, China; 2.Institute of Basic Medical
Sciences, Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing 100005, China; 3.Department of Evidence-based
Medicine and Population Genetics, Cardiovascular Institute and Fu
Wai Hospital, Chinese Academy of Medical Sciences and Peking Union
Medical College, Beijing 100037, China;Chinese National Human
Genome Center at Beijing, Beijing 100176, China; 4.Department of Epidemiology,
Tulane University School of Public Health and Tropical Medicine, New
Orleans, LA 70112, USA;Department of Medicine,
Tulane University School of Medicine, New Orleans, LA 70112, USA; 5.National Heart, Lung,
and Blood Institute, National Institute of Health, Bethesda, MD 20892,
USA; 6.Washington University
in St. Louis School of Medicine, St. Louis, MO 63110, USA; 7.University of Texas
School of Public Health, Houston, TX 77030, USA; 8.Department of Epidemiology,
Tulane University School of Public Health and Tropical Medicine, New
Orleans, LA 70112, USA; 9.Loyola University Medical
Center, Maywood, IL 60153, USA; |
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Abstract Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes. However, blood pressure (BP) responses to potassium supplementation vary among individuals. This study was designed to examine the association between 12 single nucleotide polymorphisms (SNPs) in the adducin 1 alpha (ADD1) and guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) genes and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) responses to potassium-supplementation. We conducted a 7-day high-sodium intervention (307.8 mmol sodium/day) followed by a 7-day high-sodium with potassium-supplementation (60 mmol potassium/day) among 1906 Han Chinese participants from rural north China. BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer. We identified significant associations between ADD1 variant rs17833172 and SBP, DBP, and MAP responses to potassium-supplementation (all P<0.0001) that remained significant after adjustment for multiple comparisons. In participants that were heterozygous or homozygous for the G allele of this marker, SBP, DBP, and MAP response to potassium-supplementation were −3.52 (−3.82, −3.21), −1.41 (−1.66, −1.15) and −2.12 (−2.37, −1.87), respectively, as compared to the corresponding responses of 1.99 (0.25, 3.73), −0.65 (−0.10, −0.21), and −0.23 (−0.37, 0.83), respectively, for those who were homozygous for A allele. In addition, participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation (P = 0.0041 and 0.01, respectively), which was also significant after correction for multiple testing. DBP and MAP responses to potassium-supplementation were −1.36 (−1.63, −1.10) and −2.07 (−2.32, −1.82) for those with at least G allele compared to corresponding responses of 0.86 (−0.68, 2.40) and −0.45 (−1.74, 0.84) for those who were homozygous for A allele. In summary, our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation, which could have important clinical and public health implications. Future studies aimed at replicating these novel findings are warranted.
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Keywords
blood pressure
genetics
polymorphism
die-tary potassium
potassium sensitivity
adducin 1 alpha (ADD1)
guanine nucleotide binding protein beta polypeptide 3 (GNB3)
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Issue Date: 05 March 2010
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