doi: 10.1161/hy1001.092617
(Hypertension. 2001;38:773.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Genome Scan for Blood Pressure in Dutch Dyslipidemic Families Reveals Linkage to a Locus on Chromosome 4p
From the Departments of Microbiology and Molecular Genetics (H.A., K.M.D., K.L.K., B.E.A., A.J.L.), Medicine (H.A., K.M.D., K.L.K., B.E.A., A.J.L., J.I.R.), Human Genetics (H.A., K.M.D., K.L.K., B.E.A., R.M.C., A.J.L., J.I.R.), and Pediatrics (L.S.-C.C., R.M.C., J.I.R.) and the Molecular Biology Institute (H.A., K.M.D., K.L.K., B.E.A., A.J.L.), University of California, Los Angeles; Department of Medicine, University Hospital (T.W.A.d.B., E.T.P.K.), Maastricht, The Netherlands; Department of Medicine, Harbor-UCLA Medical Center (E.I.), Torrance, Calif; and the Division of Medical Genetics, Steven Spielberg Pediatric Research Center and Cedars-Sinai Research Institute (L.S.-C.C., J.I.R.), Los Angeles, Calif.
Correspondence to Jerome I. Rotter, MD, Division of Medical Genetics, Cedars-Sinai Medical Center, 8700 W Beverly Blvd, Los Angeles, CA 90048. E-mail: jrotter{at}xchg.peds.csmc.edu
Abstract—— Genes contributing to common forms of hypertension are largely unknown. A number of studies in humans and in animal models have revealed associations between insulin resistance, dyslipidemia, and elevated hypertension. To identify genes contributing to blood pressure (BP) variation associated with insulin-resistant dyslipidemia, we conducted a genome-wide scan for BP in a set of 18 Dutch families exhibiting the common lipid disorder familial combined hyperlipidemia. Our results reveal a locus on chromosome 4 that exhibits a significant lod score of 3.9 with systolic BP. In addition, this locus also appears to influence plasma free fatty acid levels (lod=2.4). After adjustment for age and gender, the lod score for systolic BP increased to 4.6, whereas the lod score for free fatty acid levels did not change. The chromosome 4 locus contains an attractive candidate gene, 
-adducin, which has been associated with altered BP in animal studies and in some human populations. However, we found no evidence for an association between 2 intragenic -adducin polymorphisms and systolic BP in this sample. We also observed suggestive evidence for linkage (lod=1.8) of diastolic BP to the lipoprotein lipase gene locus on chromosome 8p, supporting a finding previously observed in a separate insulin-resistant population. In addition, we also obtained suggestive evidence for linkage of systolic BP (lod=2.4) and plasma apolipoprotein B levels (lod=2.0) to a locus on proximal chromosome 19p. In conclusion, our genome scan results support the existence of multiple genetic factors that can influence both BP and plasma lipid parameters.
Key Words: genetics • hypertension, essential • dyslipidemia • genome scan • linkage analysis
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