Published Online
on February 7, 2005

A more recent version of this article appeared on April 1, 2005

This Article Full Text (PDF) All Versions of this Article: 45/4/799    most recent 01.HYP.0000154786.17416.eav1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guo, X. Articles by Rotter, J. I Search for Related Content PubMed PubMed Citation Articles by Guo, X. Articles by Rotter, J. I Related Collections Risk Factors Hypertension - basic studies Type 2 diabetes Epidemiology Genetics of cardiovascular disease

Submitted on October 12, 2004
Revised on November 8, 2004

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; and 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.

^* To whom correspondence should be addressed. E-mail: Xiuqing.Guo{at}cshs.org.

Abstract--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

This article has been cited by other articles:

				F. Thameem, S. Puppala, N. H Arar, M. P Stern, J. Blangero, R. Duggirala, and H. E Abboud Endothelial nitric oxide synthase (eNOS) gene polymorphisms and their association with type 2 diabetes-related traits in Mexican Americans Diabetes and Vascular Disease Research, June 1, 2008; 5(2): 109 - 113. [Abstract] [PDF]

				P.-a. B. Shih and D. T. O'Connor Hereditary Determinants of Human Hypertension: Strategies in the Setting of Genetic Complexity Hypertension, June 1, 2008; 51(6): 1456 - 1464. [Full Text] [PDF]

				A. I. Lynch, E. Boerwinkle, B. R. Davis, C. E. Ford, J. H. Eckfeldt, C. Leiendecker-Foster, and D. K. Arnett Pharmacogenetic Association of the NPPA T2238C Genetic Variant With Cardiovascular Disease Outcomes in Patients With Hypertension JAMA, January 23, 2008; 299(3): 296 - 307. [Abstract] [Full Text] [PDF]

				C. Vassalle, M. G. Andreassi, C. Prontera, M. Fontana, L. Zyw, C. Passino, and M. Emdin Influence of ScaI and Natriuretic Peptide (NP) Clearance Receptor Polymorphisms of the NP System on NP Concentration in Chronic Heart Failure Clin. Chem., November 1, 2007; 53(11): 1886 - 1890. [Abstract] [Full Text] [PDF]

				P. Margozzini, A. Rigotti, C. Ferreccio, N. Quezada, M. Garrido, and G. Valdes Review: Hypertension and the cardiometabolic syndrome in Chile: a review of concepts and consequences for the developing world Therapeutic Advances in Cardiovascular Disease, October 1, 2007; 1(1): 83 - 90. [Abstract] [PDF]

				J.-J. Hottenga, J. B. Whitfield, D. Posthuma, G. Willemsen, E. J.C. de Geus, N. G. Martin, and D. I. Boomsma Genome-Wide Scan for Blood Pressure in Australian and Dutch Subjects Suggests Linkage at 5P, 14Q, and 17P Hypertension, April 1, 2007; 49(4): 832 - 838. [Abstract] [Full Text] [PDF]