doi: 10.1161/hc3601.096729
(Circulation. 2001;104:1255.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Coincident Linkage of Fasting Plasma Insulin and Blood Pressure to Chromosome 7q in Hypertensive Hispanic Families
From the Division of Medical Genetics (L.S.-C.C., L.J.R., S.P., J.I.R.), Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center; the Departments of Pediatrics (L.S.-C.C., L.J.R., S.P., J.I.R.), Medicine (R.C.D., N.W., M.Q., P.-Z.W., W.A.H., J.I.R.), and Human Genetics (J.I.R.), UCLA School of Medicine; and the Departments of Medicine (A.H.X., E.T., J.D., P.C.H., T.A.B.) and Preventive Medicine (A.H.X., S.P.A.), University of Southern California Keck School of Medicine, Los Angeles, Calif.
Correspondence to Li Shu-Chuan Cheng, Department of Biostatistics, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010 (E-mail lcheng{at}coh.org). Reprint requests to Jerome I. Rotter, Division of Medical Genetics, SSB 378, Cedars-Sinai Medical Center, 8723 Alden Drive, Los Angeles, CA 90048 (E-mail jrotter@xchg.peds.csmc.edu).
Background— Insulin resistance (IR) and hyperinsulinemia are phenotypically associated with hypertension. We have previously provided evidence that blood pressure (BP) and IR cosegregate in Hispanic families, suggesting that this association has a genetic component. In the present study, we provide further support for the hypothesis of a genetic basis for the BP-IR relationship from a genetic linkage study.
Methods and Results— A 10-cM genome scan was conducted in 390 Hispanic family members of 77 hypertensive probands. Detailed measurements of BP, glucose, insulin levels, and insulin sensitivity (euglycemic clamp) were performed in adult offspring of probands. Multipoint variance component linkage analysis was used. A region on chromosome 7q seemed to influence both IR and BP. The greatest evidence for linkage was found for fasting insulin (lod score=3.36 at 128 cM), followed by systolic BP (lod score=2.06 at 120 cM). Fine mapping with greater marker density in this region increased the maximum lod score for fasting insulin to 3.94 at 125 cM (P=0.00002); lod score for systolic BP was 2.51 at 112 cM. Coincident mapping at this locus also included insulin sensitivity measured by the homeostasis assessment model (HOMA) and serum leptin concentrations. Insulin sensitivity by euglycemic clamp did not map to the same locus.
Conclusions— Our results demonstrate that a major gene determining fasting insulin is located on chromosome 7q. Linkage of BP, HOMA, and leptin levels to the same region suggests this locus may broadly influence traits associated with IR and supports a genetic basis for phenotypic associations in IR syndrome.
Key Words: hypertension • insulin • genetics
This article has been cited by other articles:
 |
|
 |
|
  Y. Liu, N. Niu, X. Zhu, T. Du, X. Wang, D. Chen, X. Wu, H. F. Gu, and Y. Liu Genetic Variation and Association Analyses of the Nuclear Respiratory Factor 1 (nRF1) Gene in Chinese Patients With Type 2 Diabetes Diabetes, March 1, 2008; 57(3): 777 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Barlassina, C. Dal Fiume, C. Lanzani, P. Manunta, G. Guffanti, A. Ruello, G. Bianchi, L. Del Vecchio, F. Macciardi, and D. Cusi Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension Hum. Mol. Genet., July 1, 2007; 16(13): 1630 - 1638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. An, B. I. Freedman, S. S. Rich, S. A. Mandel, D. K. Arnett, R. H. Myers, Y.-D. I. Chen, S. C. Hunt, and D.C. Rao Quantitative Trait Loci on Chromosome 8q24 for Pancreatic {beta}-Cell Function and 7q11 for Insulin Sensitivity in Obese Nondiabetic White and Black Families: Evidence From Genome-Wide Linkage Scans in the NHLBI Hypertension Genetic Epidemiology Network (HyperGEN) Study Diabetes, February 1, 2006; 55(2): 551 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Morris Dissecting Hypertension by Obesity Identifies a Locus at 1p36 Hypertension, December 1, 2005; 46(6): 1256 - 1258. [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Mitchell, A. L. DeStefano, M. G. Larson, E. J. Benjamin, M.-H. Chen, R. S. Vasan, J. A. Vita, and D. Levy Heritability and a Genome-Wide Linkage Scan for Arterial Stiffness, Wave Reflection, and Mean Arterial Pressure: The Framingham Heart Study Circulation, July 12, 2005; 112(2): 194 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-F. Chiu, L.-M. Chuang, C.-F. Hsiao, Y.-J. Hung, M.-W. Lin, Y.-T. Chen, J. Grove, E. Jorgenson, T. Quertermous, N. Risch, et al. An Autosomal Genome-wide Scan for Loci Linked to Pre-Diabetic Phenotypes in Nondiabetic Chinese Subjects From the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance Family Study Diabetes, April 1, 2005; 54(4): 1200 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Guo, S. Cheng, K. D. Taylor, J. Cui, R. Hughes, M. J. Quinones, I. Bulnes-Enriquez, R. De La Rosa, G. Aurea, H. Yang, et al. Hypertension Genes Are Genetic Markers for Insulin Sensitivity and Resistance Hypertension, April 1, 2005; 45(4): 799 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. An, B. I. Freedman, C. L. Hanis, Y.-D. I. Chen, A. B. Weder, N. J. Schork, E. Boerwinkle, M. A. Province, C. A. Hsiung, X. Wu, et al. Genome-wide Linkage Scans for Fasting Glucose, Insulin, and Insulin Resistance in the National Heart, Lung, and Blood Institute Family Blood Pressure Program: Evidence of Linkages to Chromosome 7q36 and 19q13 From Meta-Analysis Diabetes, March 1, 2005; 54(3): 909 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Rich, D. W. Bowden, S. M. Haffner, J. M. Norris, M. F. Saad, B. D. Mitchell, J. I. Rotter, C. D. Langefeld, C. C. Hedrick, L. E. Wagenknecht, et al. A Genome Scan for Fasting Insulin and Fasting Glucose Identifies a Quantitative Trait Locus on Chromosome 17p: The Insulin Resistance Atherosclerosis Study (IRAS) Family Study Diabetes, January 1, 2005; 54(1): 290 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. El-Atat, S. N. Stas, S. I. McFarlane, and J. R. Sowers The Relationship between Hyperinsulinemia, Hypertension and Progressive Renal Disease J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2816 - 2827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Rich, D. W. Bowden, S. M. Haffner, J. M. Norris, M. F. Saad, B. D. Mitchell, J. I. Rotter, C. D. Langefeld, L. E. Wagenknecht, and R. N. Bergman Identification of Quantitative Trait Loci for Glucose Homeostasis: The Insulin Resistance Atherosclerosis Study (IRAS) Family Study Diabetes, July 1, 2004; 53(7): 1866 - 1875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Gibbons, C. C. Liew, M. O. Goodarzi, J. I. Rotter, W. A. Hsueh, H. M. Siragy, R. Pratt, and V. J. Dzau Genetic Markers: Progress and Potential for Cardiovascular Disease Circulation, June 29, 2004; 109(25_suppl_1): IV-47 - IV-58. [Full Text] [PDF]
|
|
|
|
|
|
W.-D. Li, C. Dong, D. Li, H. Zhao, and R. A. Price An Obesity-Related Locus in Chromosome Region 12q23-24 Diabetes, March 1, 2004; 53(3): 812 - 820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. F. Loos, P. T. Katzmarzyk, D. C. Rao, T. Rice, A. S. Leon, J. S. Skinner, J. H. Wilmore, T. Rankinen, and C. Bouchard Genome-Wide Linkage Scan for the Metabolic Syndrome in the HERITAGE Family Study J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5935 - 5943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Camp, P. N. Hopkins, S. J. Hasstedt, H. Coon, A. Malhotra, R. M. Cawthon, and S. C. Hunt Genome-Wide Multipoint Parametric Linkage Analysis of Pulse Pressure in Large, Extended Utah Pedigrees Hypertension, September 1, 2003; 42(3): 322 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Bergman, D. J. Zaccaro, R. M. Watanabe, S. M. Haffner, M. F. Saad, J. M. Norris, L. E. Wagenknecht, J. E. Hokanson, J. I. Rotter, and S. S. Rich Minimal Model-Based Insulin Sensitivity Has Greater Heritability and a Different Genetic Basis Than Homeostasis Model Assessment or Fasting Insulin Diabetes, August 1, 2003; 52(8): 2168 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-D. Li, D. Li, S. Wang, S. Zhang, H. Zhao, and R. A. Price Linkage and Linkage Disequilibrium Mapping of Genes Influencing Human Obesity in Chromosome Region 7q22.1-7q35 Diabetes, June 1, 2003; 52(6): 1557 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Lakka, T. Rankinen, S. J. Weisnagel, Y. C. Chagnon, T. Rice, A. S. Leon, J. S. Skinner, J. H. Wilmore, D.C. Rao, and C. Bouchard A Quantitative Trait Locus on 7q31 for the Changes in Plasma Insulin in Response to Exercise Training: The HERITAGE Family Study Diabetes, June 1, 2003; 52(6): 1583 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Monti, C. Barlassina, L. Citterio, E. Galluccio, C. Berzuini, E. Setola, G. Valsecchi, P. Lucotti, G. Pozza, L. Bernardinelli, et al. Endothelial Nitric Oxide Synthase Polymorphisms Are Associated With Type 2 Diabetes and the Insulin Resistance Syndrome Diabetes, May 1, 2003; 52(5): 1270 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Henry, F. Thomas, A. Benetos, and L. Guize Impaired Fasting Glucose, Blood Pressure and Cardiovascular Disease Mortality Hypertension, October 1, 2002; 40(4): 458 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Hunt, R. C. Ellison, L. D. Atwood, J. S. Pankow, M. A. Province, and M. F. Leppert Genome Scans for Blood Pressure and Hypertension: The National Heart, Lung, and Blood Institute Family Heart Study Hypertension, July 1, 2002; 40(1): 1 - 6. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Xiang, S. P. Azen, T. A. Buchanan, L. J. Raffel, S. Tan, L.S.-C. Cheng, J. Diaz, E. Toscano, M. Quinonnes, C.R. Liu, et al. Heritability of Subclinical Atherosclerosis in Latino Families Ascertained Through a Hypertensive Parent Arterioscler Thromb Vasc Biol, May 1, 2002; 22(5): 843 - 848. [Abstract] [Full Text] [PDF]
|
|