Tohoku J. Exp. Med., 2007, 213(3)

Gene Polymorphisms of the Renin-Angiotensin-Aldosterone System and Angiotensin II Type 1-Receptor Activating Antibodies in Renal Rejection

GENG ZHANG,¹ HE WANG,¹ FULI WANG,¹ LEI YU,¹ XIAOJIAN YANG,¹ JUNHUA MENG,¹ WEIJUN QIN,¹ GUOJUN WU,¹ JIANHUA LI,¹ ANGANG YANG,^2,3 YU ZHOU¹ and RUI ZHANG²

¹Department of Urology, Xijing Hospital, Xi'an, China
²Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China
³Department of Immunology, Fourth Military Medical University, Xi'an, China

Steroid refractory acute rejection (SRAR) is a major vital factor in renal transplantation recipients. The pathogenesis of SRAR may involve both immune and non-immune mechanisms. A decreased renal allograft function has also been associated with increased activity of renin-angiotensin-aldosterone system (RAS), which may be genetically determined. A total 206 renal transplant recipients, 116 males and 90 females, were included. The effects of gene polymorphisms of the four components of RAS including angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin type 1 receptor (AT1R), and aldosterone synthase (CYP11B2) were investigated in19 cases of renal transplant patients with SRAR. The association between SRAR and the activating antibodies targeting the AT1R were also investigated. Genotyping was performed for the M235T-AGT, the I/D-ACE, the A1166C-AT1R, and the -344T/C-CYP11B2 gene polymorphisms using polymerase chain reaction. Our results showed that renal allograft recipients with SRAR had significantly higher occurrences of the DD genotype of ACE and CC genotype of AT1R than recipients without SRAR. The other genetic polymorphisms of the RAS were not associated with SRAR. Activating antibodies targeting the AT1R were detected in the sera from 14 SRAR victims with malignant hypertension and without anti-HLA antibodies. This study provides evidence that determination before transplantation of the polymorphism of the gene encoding components of RAS may help identify patients who are at risk for SRAR. The detection of the antibodies of AT1R may contribute to the prevention of SRAR.

keywords —— antibody; polymorphism; renin-angiotensin-aldosterone system; steroid refractory acute rejection; AT1-AA

© 2007 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2007, 213, 203-214

Correspondence: Geng Zhang, Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

e-mail: zhangg@fmmu.edu.cn