Published Online
on September 27, 2004

A more recent version of this article appeared on November 1, 2004

This Article Full Text (PDF) All Versions of this Article: 44/5/681    most recent 01.HYP.0000144294.28985.d5v1 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 Franks, P. W. Articles by Hanson, R. L. Search for Related Content PubMed PubMed Citation Articles by Franks, P. W. Articles by Hanson, R. L. Related Collections Clinical genetics Obesity Type 2 diabetes Clinical Studies Other etiology Epidemiology Other Vascular biology

Submitted on July 1, 2004
Revised on July 21, 2004

Interaction Between an 11HSD1 Gene Variant and Birth Era Modifies the Risk of Hypertension in Pima Indians

Paul W. Franks^*; William C. Knowler; Saras Nair; Juraj Koska; Yong-Ho Lee; Robert S. Lindsay; Brian R. Walker; Helen C. Looker; Paska A. Permana; P. Antonio Tataranni; and Robert L. Hanson

From the Phoenix Epidemiology and Clinical Research Branch (P.W.F., W.C.K., S.N., J.K., Y.-H.L., H.C.L., P.A.T., R.L.H.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Ariz; the Division of Cardiovascular and Medical Sciences (R.S.L.), Gardiner Institute, Western Infirmary, University of Glasgow, Glasgow, Scotland; the Endocrinology Unit (B.R.W.), University of Edinburgh, Western General Hospital, Edinburgh, Scotland; and the Carl T. Hayden VA Medical Center (P.A.P.), Phoenix, Ariz.

^* To whom correspondence should be addressed. E-mail: pfranks{at}niddk.nih.gov.

Abstract--11-Hydroxysteroid dehydrogenase type 1 (11HSD1) is a candidate gene for hypertension, diabetes, and obesity through altered glucocorticoid production. This study explored the association of 11HSD1 gene variants with diabetes, hypertension, and obesity in a longitudinal population study of American Indians (N=918; exams=5508). In multivariate mixed models assuming an additive effect of genotype, a 5' upstream variant (rs846910) was associated with blood pressure (diastolic blood pressure =1.58 mm Hg per copy of the A allele, P=0.0008; systolic blood pressure =2.28 mm Hg per copy of the A allele, P=0.004; mean arterial blood pressure =1.83 mm Hg per copy of the A allele, P=0.0006) and hypertension (odds ratio=1.27 per copy of the A allele, P=0.02). However, birth date modified these associations (test for interaction: diastolic blood pressure P=0.16; systolic blood pressure P=0.007; mean arterial blood pressure P=0.01), such that the magnitude and direction of association between genotype and blood pressure changed with time. Finally, in models controlling for potential confounding by population stratification, we observed evidence of within-family effects for blood pressure (diastolic blood pressure =1.77 mm Hg per copy of the A allele, P=0.004; systolic blood pressure =2.04 mm Hg per copy of the A allele, P=0.07; mean arterial blood pressure =1.85 mm Hg per copy of the A allele, P=0.01) and for hypertension (odds ratio=1.26 per copy of the A allele; P=0.08). No association was observed for obesity. Associations with diabetes were similar in magnitude as reported previously but were not statistically significant. These data demonstrate association between genetic variability at 11HSD1 with hypertension, but these effects are modified by environmental factors.

Key words: genetics • epidemiology • blood pressure • nutrition • gene expression

This article has been cited by other articles:

				Y. Liu, D. Mladinov, J. L. Pietrusz, K. Usa, and M. Liang Glucocorticoid response elements and 11{beta}-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression Cardiovasc Res, January 1, 2009; 81(1): 140 - 147. [Abstract] [Full Text] [PDF]

				Y. Liu, R. J. Singh, K. Usa, B. C. Netzel, and M. Liang Renal medullary 11{beta}-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension Physiol Genomics, December 12, 2008; 36(1): 52 - 58. [Abstract] [Full Text] [PDF]

				K. S. Vimaleswaran, J. Luan, G. Andersen, Y. L. Muller, E. Wheeler, E. C. Brito, S. O'Rahilly, O. Pedersen, L. J. Baier, W. C. Knowler, et al. The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals J Appl Physiol, October 1, 2008; 105(4): 1352 - 1358. [Abstract] [Full Text] [PDF]

				D. P Macfarlane, S. Forbes, and B. R Walker Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome J. Endocrinol., May 1, 2008; 197(2): 189 - 204. [Abstract] [Full Text] [PDF]

				B. R Walker Glucocorticoids and Cardiovascular Disease Eur. J. Endocrinol., November 1, 2007; 157(5): 545 - 559. [Abstract] [Full Text] [PDF]

				A. Gambineri, V. Vicennati, S. Genghini, F. Tomassoni, U. Pagotto, R. Pasquali, and B. R. Walker Genetic Variation in 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Predicts Adrenal Hyperandrogenism among Lean Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2295 - 2302. [Abstract] [Full Text] [PDF]