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Original Article

Relationships Between Selected Gene Polymorphisms and Blood Pressure Sensitivity to Weight Loss in Elderly Persons With Hypertension

William J. Kostis, Javier Cabrera, W. Craig Hooper, Paul K. Whelton, Mark A. Espeland, Nora M. Cosgrove, Jerry Q. Cheng, Yingzi Deng, Christine De Staerck, Meredith Pyle, Nisa Maruthur, Ingrid Reyes, Cheryl A.M. Anderson, Jie Liu, John B. Kostis
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https://doi.org/10.1161/HYPERTENSIONAHA.111.00712
Hypertension. 2013;HYPERTENSIONAHA.111.00712
Originally published February 25, 2013
William J. Kostis
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Javier Cabrera
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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W. Craig Hooper
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Paul K. Whelton
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Mark A. Espeland
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Nora M. Cosgrove
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Jerry Q. Cheng
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Yingzi Deng
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Christine De Staerck
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Meredith Pyle
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Nisa Maruthur
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Ingrid Reyes
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Cheryl A.M. Anderson
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Jie Liu
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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John B. Kostis
From the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA (W.J.K.); Department of Statistics, Rutgers University, Piscataway, NJ (J.C., I.R., J.L.); Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (J.C., N.M.C., J.Q.C., Y.D., J.B.K.); Centers for Disease Control and Prevention, Atlanta, GA (W.C.H., C.D.S., M.P.); Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.); Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (N.M.); and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (N.M., C.A.M.A.).
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Abstract

Salt sensitivity, the heterogeneity in the response of blood pressure (BP) to alterations in sodium intake, has been studied extensively, whereas weight sensitivity, the heterogeneity in BP response to weight change, has received scant attention. We examined the relationship of 21 gene polymorphisms previously found to be associated with hypertension, diabetes mellitus, or obesity, with weight sensitivity in the Trial of Nonpharmacologic Interventions in the Elderly, where participants with hypertension were randomized to receive intensive dietary intervention of sodium reduction, weight loss, both, or attention control, whereas pharmacological therapy was kept constant. After correcting for multiplicity, we identified significant associations of 3 polymorphisms with weight sensitivity of systolic BP (rs4646994, rs2820037, and rs1800629) and 3 polymorphisms for diastolic BP (rs4646994, rs2820037, and rs5744292). A recursive partitioning algorithm selected the combination of rs4646994, rs1800629, rs1982073, and rs1800896 as the set associated with the highest weight sensitivity. Polymorphisms related to hypertension, obesity, and diabetes mellitus are associated with weight sensitivity of BP.

  • blood pressure
  • genetics
  • obesity
  • sodium
  • Received November 25, 2012.
  • Revision received January 14, 2013.
  • Accepted February 4, 2013.
  • © 2013 American Heart Association, Inc.
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    Relationships Between Selected Gene Polymorphisms and Blood Pressure Sensitivity to Weight Loss in Elderly Persons With Hypertension
    William J. Kostis, Javier Cabrera, W. Craig Hooper, Paul K. Whelton, Mark A. Espeland, Nora M. Cosgrove, Jerry Q. Cheng, Yingzi Deng, Christine De Staerck, Meredith Pyle, Nisa Maruthur, Ingrid Reyes, Cheryl A.M. Anderson, Jie Liu and John B. Kostis
    Hypertension. 2013;HYPERTENSIONAHA.111.00712, originally published February 25, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.111.00712

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    Relationships Between Selected Gene Polymorphisms and Blood Pressure Sensitivity to Weight Loss in Elderly Persons With Hypertension
    William J. Kostis, Javier Cabrera, W. Craig Hooper, Paul K. Whelton, Mark A. Espeland, Nora M. Cosgrove, Jerry Q. Cheng, Yingzi Deng, Christine De Staerck, Meredith Pyle, Nisa Maruthur, Ingrid Reyes, Cheryl A.M. Anderson, Jie Liu and John B. Kostis
    Hypertension. 2013;HYPERTENSIONAHA.111.00712, originally published February 25, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.111.00712
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