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(Hypertension. 2005;45:799.)
© 2005 American Heart Association, Inc.

Original Articles

Hypertension Genes Are Genetic Markers for Insulin Sensitivity and Resistance

Xiuqing Guo; Suzanne Cheng; Kent D. Taylor; Jinrui Cui; Randall Hughes; Manuel J. Quiñones; Isabel Bulnes-Enriquez; Roxana De La Rosa; George Aurea; Huiying Yang; Willa Hsueh; Jerome I Rotter

From the Medical Genetics Institute (X.G., K.D.T., J.C., H.Y., J.I.R.), Spielberg Pediatrics Research Center, Cedars-Sinai Medical Center; the Department of Pediatrics (X.G., K.D.T., H.Y., J.I.R.) and the Department of Medicine (M.J.Q., I.B.-E., R.D.L.R., G.A., W.H.), David Geffen School of Medicine at UCLA, Los Angeles, Calif; and the Department of Human Genetics (S.C., R.H.), Roche Molecular Systems Inc, Alameda, Calif.

Correspondence to Xiuqing Guo, PhD, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Room 378, Los Angeles, CA 90048. E-mail Xiuqing.Guo{at}cshs.org

Insulin resistance is a determinant of blood pressure variation and risk factor for hypertension. Because insulin resistance and blood pressure cosegregate in Mexican American families, we thus investigated the association between variations in 9 previously reported hypertension genes (ACE, AGT, AGTRI, ADDI, NPPA, ADDRB2, SCNN1A, GNB3, and NOS3) and insulin resistance. Families were ascertained via a coronary artery disease proband in the Mexican American Coronary Artery Disease Project. Individuals from 100 Mexican American families (n=656) were genotyped for 14 polymorphisms in the 9 genes and all adult offspring and offspring spouses were phenotyped for insulin sensitivity by hyperinsulinemic euglycemic clamp (n=449). AGT M235T and NOS3 A(–922)G and E298D polymorphisms were significantly associated with insulin sensitivity (P=0.018, 0.036, 0.039) but were not significant after adjusting for body mass index. ADD1 G460W was associated with insulin sensitivity only after adjusting for body mass index. The NPPA T2238C and SCNN1A A663T were associated with decreased fasting insulin levels after adjusting for body mass index (P=0.015 and 0.028). In conclusion, AGT, NOS3, NPPA, ADRB2, ADD1, and SCNN1A may well be genetic markers for insulin resistance, and adiposity was a potential modifier for only some gene/trait combinations. Our data support the hypothesis that genes in the blood pressure pathway may play a role in insulin resistance in Mexican Americans.

Key Words: genetics • hypertension • insulin resistance • risk factors

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