title: Gene polymorphisms of the renin-angiotensin-aldosterone system and angiotensin II type 1-receptor activating antibodies in renal rejection.
abstract: 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 in 19 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.
authors.affiliation: Department of Urology, Xijing Hospital, Xi'an, china. zhangg@fmmu.edu.cn
authors.forename: Geng
authors.initials: G
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Fuli
authors.initials: F
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Yang
authors.forename: Junhua
authors.initials: J
authors.lastname: Meng
authors.forename: Weijun
authors.initials: W
authors.lastname: Qin
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D005260:Female; D006084:Graft Rejection; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000628:therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007674:Kidney Diseases / Q000235:genetics*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D007166:Immunosuppressive Agents; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A