(Hypertension. 2000;36:2.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Combinations of Variations in Multiple Genes Are Associated With Hypertension
From the Departments of Microbiology (S.M.W., M.D., F.E., M.M.M.) and Anatomy and Physiology (P.E., A.A.), Meharry Medical College, Nashville, Tenn; Department of Medicine and Therapeutics (J.H.A., J.K., J.A.), University of Ghana Medical School, Accra, Ghana; Division of Medical Genetics (J.A.P.), Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn; Department of Anatomy and Occlusion (H.J.), School of Dentistry, Meharry Medical College, Nashville, Tenn; School of Medicine (K.J.), Meharry Medical College, Nashville, Tenn; Institute for Human and Molecular Genetics (L.-J.W.) and Department of Pediatrics and Physiology and Biophysics (P.A.J.), Georgetown University Medical Center, Washington, DC; and Department of Pathology (R.A.F.), Medical Automation Research Center, University of Virginia Health Sciences Center, Charlottesville.
Correspondence to Dr Scott M Williams, Department of Microbiology, Meharry Medical College, Nashville, TN 37208-3599. E-mail smwilliams{at}mail.mmc.edu
Abstract—The genetic analysis of hypertension has revealed complex and inconsistent results, making it difficult to draw clear conclusions regarding the impact of specific genes on blood pressure regulation in diverse human populations. Some of the confusion from previous studies is probably due to undetected gene-gene interactions. Instead of focusing on the effects of single genes on hypertension, we examined the effects of interactions of alleles at 4 candidate loci. Three of the loci are in the renin-angiotensin-system, angiotensinogen, ACE, and angiotensin II type 1 receptor, and they have been associated with hypertension in at least 1 previous study. The fourth locus studied is a previously undescribed locus, named FJ. In total, 7 polymorphic sites at these loci were analyzed for their association with hypertension in 51 normotensive and 126 hypertensive age-matched individuals. There were no significant differences between the 2 phenotypic classes with respect to either allele or genotype frequencies. However, when we tested for nonallelic associations (linkage disequilibrium), we found that of the 120 multilocus comparisons, 16 deviated significantly from random in the hypertensive class, but there were no significant deviations in the normotensive group. These findings suggest that genetic interactions between multiple loci rather than variants of a single gene underlie the genetic basis of hypertension in our study subjects. We hypothesize that such interactions may account for the inconsistent findings in previous studies because, unlike our study, prior studies almost always examined single-locus effects and did not consider the effects of variation at other potentially interacting loci.
Key Words: hypertension, essential • genes • renin-angiotensin system • receptors, angiotensin II • angiotensinogen • blacks • ethnic groups
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