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Published online April 19, 2007
Diabetes 56:1905-1912, 2007
DOI: 10.2337/db06-1127
© 2007 by the American Diabetes Association
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Effects of the Renin-Angiotensin System Genes and Salt Sensitivity Genes on Blood Pressure and Atherosclerosis in the Total Population and Patients With Type 2 Diabetes

Mojgan Yazdanpanah1, Yuri S. Aulchenko1, Albert Hofman1, Joop A.M.J.L. Janssen2, Fakhredin A. Sayed-Tabatabaei1, Ron H.N. van Schaik3, Olaf H. Klungel4, Bruno H.C.H. Stricker1, Huibert A.P. Pols1,2, Jacqueline C.M. Witteman1, Steven W.J. Lamberts2, Ben A. Oostra1, and Cornelia M. van Duijn1

1 Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics and Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands
2 Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
3 Department of Clinical Chemistry, Erasmus Medical Centre, Rotterdam, the Netherlands
4 Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands

Address correspondence and reprint requests to Prof. Dr. Cornelia M. van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, Netherlands. E-mail: c.vanduijn{at}erasmusmc.nl

Abbreviations: IMT, intima-media thickness; RAS, renin-angiotensin system

Most studies on the genetic determinants of blood pressure and vascular complications of type 2 diabetes have focused on the effects of single genes. These studies often have yielded conflicting results. Therefore, we examined the combined effects of three renin-angiotensin system (RAS) genes and three salt sensitivity genes in relation to blood pressure and atherosclerosis in the total population and type 2 diabetic patients. The study was a part of the Rotterdam Study, a population-based cohort study. We have genotyped three RAS gene polymorphisms and three salt sensitivity gene polymorphisms. Diabetic patients with three risk genotypes of the RAS genes had a 6.9 mmHg higher systolic blood pressure (P for trend = 0.04) and a 6.0 mmHg higher pulse pressure (P for trend = 0.03) than those who did not carry any risk genotypes. Diabetic patients with three risk genotypes of the salt sensitivity genes had a 9.0 mmHg higher systolic blood pressure (P = 0.19) and a 13.1 mmHg higher pulse pressure (P = 0.02). Diabetic patients who carried three risk genotypes for the RAS genes had a higher mean intima-media thickness than those with two risk genotypes (mean difference 0.04 mm, P = 0.02). We found that among type 2 diabetic patients, mean systolic blood pressure, pulse pressure, and risk of hypertension increased with the number of risk genotypes for the RAS genes and the salt sensitivity genes.


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Copyright © 2007 by the American Diabetes Association.