Published Online
on December 2, 2002

A more recent version of this article appeared on January 1, 2003

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Submitted on May 6, 2002
Revised on June 6, 2002

Angiotensinogen Gene Haplotype and Hypertension. Interaction With ACE Gene I Allele

Chia-Ti Tsai; Daniele Fallin; Fu-Tien Chiang^*; Juey-Jen Hwang; Ling-Ping Lai; Kuan-Lih Hsu; Chuen-Den Tseng; Chiau-Suong Liau; and Yung-Zu Tseng

From the Division of Cardiology, Department of Internal Medicine (C.-T.T., F.-T.C., J.-J.H., L.-P.L., K.-L.H., C.-D.T., C.-S.L., Y.-Z.T.) and Department of Laboratory Medicine (F.-T.C.), National Taiwan University Hospital, Taipei, Taiwan; and Department of Epidemiology and Biostatistics, Case Western Reserve University (D.F.), Cleveland, Ohio.

^* To whom correspondence should be addressed. E-mail: futienc{at}ha.mc.ntu.edu.tw.

Abstract—There are many reports demonstrating the association of renin-angiotensin system gene polymorphisms with hypertension in different populations. In the present study, we used haplotype analyses of the angiotensinogen gene with a new permutation-based hypothesis testing method to determine the association between multilocus angiotensinogen gene polymorphisms and hypertension in a relatively homogeneous Taiwanese population. We also genotyped angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin II type 1-receptor gene A1166C polymorphism to detect epistatic gene-gene interactions. There were 408 patients with hypertension (hypertensives) and 286 controls. The angiotensinogen gene haplotype frequencies were significantly different between hypertensives and controls, and this finding was only present in subjects with angiotensin-converting enzyme gene II genotypes when the analysis was stratified by genotype of this polymorphism. In addition, the angiotensinogen gene haplotype structure of hypertensives was more heterogeneous than that of controls. Our results showed that angiotensinogen gene haplotypes were associated with hypertension and might act synergistically with I allele of the angiotensin-converting enzyme gene.

Key words: haplotypes • hypertension, genetic • polymorphism • genetics • angiotensinogen • angiotensin-converting enzyme • receptors, angiotensin II

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