title: Association of MYH9 rs3752462 and rs5756168 Polymorphisms With Transplanted Kidney Artery Stenosis.
abstract: Allelic variants of the MYH9 gene, encoding myosin nonmuscle heavy chain type IIA, have been shown to correlate with diminished glomerular filtration rates and end-stage kidney disease in individuals of Caucasian ancestry. Myosin nonmuscle heavy chain type IIA is expressed during development as well as in injured vessels and kidney structures. We hypothesized that MYH9 risk variants may correlate with kidney artery injury and dysfunctional healing, such as transplant renal artery stenosis (TRAS). Our study aimed at evaluating the association of MYH9 risk allelic variants (rs4821480, rs4821481, rs3752462, rs11089788, rs136211, rs5756168, rs2032487, and rs2239784) with TRAS, defined as >50% renal artery lumen reduction. Genotyping was performed with the use of custom Taqman genotyping assays on DNA samples (n = 295) from white deceased-donor kidney transplant recipients and genomic DNA from the corresponding donors. Statistical analysis was performed with the use of Kaplan-Meier estimates, log-rank tests, and proportional hazard Cox models. Recipients carrying TT in rs5756168 experienced diminished risk of TRAS (hazard ratio [HR], 0.31; P < .009), whereas organs carrying CC in rs3752462 were exposed to excessive TRAS risk (HR, 2.54; P < .047). In multivariate stepwise analysis TRAS was 10.9-fold increased in kidneys originating from rs3752462 CC, whereas the risk was decreased 3.45-fold (adjusted HR, 0.29) in recipients carrying rs5756168 TT (P < .007 and P < .033, respectively). Intracranial bleeding or trauma compared with other mechanisms of donor death diminished TRAS risk by 87% and 91%, respectively (P < .030 and P < .017). Our study is the first to identify genetic predisposition to transplant renal artery stenosis.
authors: Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors: J
authors: J
authors: Pazik
authors: Department of Epidemiology, Medical University of Warsaw, Warsaw, Poland.
authors: Z
authors: Z
authors: Lewandowski
authors: Institute of Physiology and Pathology of Hearing, Warsaw, Poland.
authors: M
authors: M
authors: Oldak
authors: Institute of Physiology and Pathology of Hearing, Warsaw, Poland.
authors: D
authors: D
authors: Oziębło
authors: Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors: A
authors: A
authors: Perkowska Ptasinska
authors: Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors: A
authors: A
authors: Sadowska
authors: Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland. Electronic address: ewnowacka@wp.pl.
authors: E
authors: E
authors: Nowacka-Cieciura
authors: Department of Clinical Immunology, Medical University of Warsaw, Warsaw, Poland.
authors: M
authors: M
authors: Nowaczyk
authors: Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
authors: J
authors: J
authors: Malejczyk
authors: Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland.
authors: A
authors: A
authors: Kwiatkowski
authors: Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors: M
authors: M
authors: Durlik
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D024462:Myosin Type II / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012078:Renal Artery Obstruction / Q000235:genetics* / Q000401:mortality
chemical_list: D024462:Myosin Type II