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(Hypertension. 2002;40:634.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Identification of Hypertension-Related QTLs in African American Sib Pairs

Theodore A. Kotchen; Ulrich Broeckel; Clarence E. Grim; Pavel Hamet; Howard Jacob; Mary L. Kaldunski; Jane Morley Kotchen; Nicholas J. Schork; Peter J. Tonellato; Allen W. Cowley, Jr

From the Departments of Medicine (T.A.K., U.B., C.E.G.) and Physiology (H.J., M.L.K., P.J.T., A.W.C.), and the Division of Epidemiology, Health Policy Institute (J.M.K.), Medical College of Wisconsin, Milwaukee; Centre Hospitalier of the University of Montreal (P.H.), Montreal, Quebec, Canada; and Department of Psychiatry, University of California at San Diego (N.J.S.), La Jolla.

Correspondence to Theodore A. Kotchen, MD, Department of Medicine, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226. E-mail tkotchen{at}mcw.edu

To link hypertension-related phenotypes with chromosomal loci, genome scans were performed in 150 African American sib pairs concordant for essential hypertension. Phenotypes included blood pressure, anthropomorphic measurements, and estimates of body fluid compartments as determined by impedance plethysmography. These phenotypes were also measured in 335 normotensive African Americans. Phenotypes with LOD scores >3.3 were further evaluated for significance by use of permutation procedures. Significant linkage was detected for body mass index (BMI) on chromosomes 1 and 8 and for the ratio of extracellular water to total body water (ECF/TBW) on chromosomes 3, 5, 6, and 7. Both BMI and ECF/TBW were greater in hypertensive sibs than in normotensive subjects (P<0.001). In a subset of hypertensive sibs and normotensive subjects, average 24-hour blood pressures were correlated with ECF/TBW (P<0.01). A region linked to BMI in the hypertensive sibs corresponds to a region of conserved synteny containing blood pressure–related QTLs in an F2 cross of Brown NorwayxDahl salt-sensitive rats. Focusing on hypertension-related phenotypes is a promising approach for identifying the genetic determinants of hypertension.

Key Words: blacks • body mass index • comparative mapping • genome scan • plethysmography

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