Published online before print January 12, 2004, doi: 10.1161/01.HYP.0000112303.26158.92
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(Hypertension. 2004;43:483.)
© 2004 American Heart Association, Inc.
Scientific Contribution |
Heritability of Leukoaraiosis in Hypertensive Sibships
From the Division of Hypertension, Department of Internal Medicine (S.T.T.), Division of Biostatistics, Department of Health Sciences Research (M.D.A.), and Department of Diagnostic Radiology (C.R.J.), Mayo Clinic and Foundation, Rochester, Minn; Department of Medicine (T.H.M.), University of Mississippi, Jackson; and Human Genetics Center and Institute of Molecular Medicine (M.F., E.B.), University of Texas-Houston Health Science Center, Houston.
Correspondence to Dr Stephen T. Turner, Division of Hypertension, Mayo Clinic, 200 First Street SW, Rochester MN 55905. E-mail turner.stephen{at}mayo.edu
Ischemic damage to the subcortical white matter of the brain, referred to as leukoaraiosis, is a frequent complication of hypertension-related microvascular disease and contributes to the risk of stroke and vascular dementia. A large genetic contribution to this late-life form of target organ damage was suggested by a study of elderly male twins. As part of the Genetic Epidemiology Network of Arteriopathy (GENOA), 483 non-Hispanic white subjects were recruited to undergo MRI for determination of the brain volume of leukoaraiosis (291 women and 192 men from 210 sibships providing 434 sibling pairs; mean age±SD=65.2±7.3 years). The GENOA–Rochester sibships contain 2 or more siblings with essential hypertension diagnosed before age 60. The frequency distribution of the volume of leukoaraiosis was positively skewed, with a median value of 6.61 cm3 (interquartile range: 4.77 to 9 0.83 cm3). Variance component models were used to estimate the heritability (ie, the proportion of phenotypic variation caused by additive genetic factors). After logarithm transformation of the volume of leukoaraiosis, the estimated heritability (±SE) was 0.802±0.102 (P<0.0001). Adjustments for sex, age, systolic blood pressure, and brain volume reduced the heritability estimate to 0.671±0.110 (P<0.0001). This evidence of strong genetic influence on the susceptibility to leukoaraiosis justifies efforts to localize the responsible genes and characterize the predisposing genetic polymorphisms.
Key Words: blood pressure • hypertension, genetic • genetics • brain • ischemia
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