(Circulation. 2001;103:78.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Evidence for Joint Genetic Control of Insulin Sensitivity and Systolic Blood Pressure in Hispanic Families With a Hypertensive Proband
From the Department of Preventive Medicine (A.H.X., S.P.A., S.T.), the Atherosclerosis Research Unit (S.P.A., H.N.H.), and the Department of Medicine (J.D., E.T., P.C.H., H.N.H., T.A.B.), University of Southern California Keck School of Medicine, Los Angeles, Calif; the Division of Medical Genetics (L.J.R., L.S.-C.C., J.I.R.), Departments of Medicine and Pediatrics, Cedars-Sinai Medical Center, Los Angeles, Calif; and the Departments of Medicine (W.A.H., J.I.R.), Pediatrics (L.J.R., J.I.R.), and Human Genetics (J.I.R.), University of California at Los Angeles Medical School.
Correspondence to Thomas A. Buchanan, MD, Room 6602, General Hospital, 1200 N State St, Los Angeles, CA 90089-9317. E-mail buchanan{at}hsc.usc.edu
Background—The clustering of hypertension, insulin resistance, and obesity remains unexplained. We tested for genetic and nongenetic influences on the association among these traits in Hispanic families with hypertension.
Methods and Results—Blood pressure and body mass index (BMI) were measured in 331 members of 73 Hispanic families in which an index case (proband) had hypertension. Insulin sensitivity (SI) was measured by euglycemic clamp in 287 probands and their spouses (parents’ generation) or their adult offspring. Correlation analysis examined relationships among traits within and between generations. Path analysis estimated genetic and nongenetic contributions to variability in systolic blood pressure (SBP), SI, and the correlation between them. In the offspring, there was a significant correlation between individuals for each trait, as well as significant correlations within and between individuals for all possible pairs of traits. Between generations, SBP, SI, and BMI in parents correlated with the same traits in their offspring; BMI in parents correlated with SI and SBP in offspring; and SI in parents correlated with SBP in offspring. Path analysis estimated that among offspring, genetic effects unrelated to BMI accounted for 60.8% of the variation in SBP, 36.8% of the variation in SI, and 31.5% of the correlation between SBP and SI after adjustment for age and sex. Heritable effects related to BMI accounted for an additional 14.0% of variation in SBP, 26.8% of variation in SI, and 56.3% of variation in their correlation.
Conclusions—Clustering of hypertension and insulin resistance in Hispanic Americans is accounted for in part by heritable factors both associated with and independent of BMI.
Key Words: blood pressure • insulin • obesity • genetics • risk factors
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