title: Genotype polymorphisms of genes regulating nitric oxide synthesis determine long-term arteriovenous fistula patency in male hemodialysis patients.
abstract: OBJECTIVE
  Nitric oxide (NO) is a pivotal vasoactive substance modulating arteriovenous fistula (AVF) patency for hemodialysis (HD). Since genetic background could be the predicting factor of AVF malfunction, we aimed to investigate whether the NO-related genotype polymorphisms determine AVF survival rates.
  
  
  METHODS
  This is a retrospective, observational, multi-center study involving eight HD units in Taiwan, enrolled 580 patients initiating maintenance HD via AVFs. Genotype polymorphisms of NO-biosynthesis regulating enzymes (DDAH-1, DDAH-2, eNOS and PRMT1) were compared between HD patients with (n = 161) and without (n = 419) history of AVF malfunction. Subgroup analyses by gender were performed to evaluate the genetic effect in difference sexes.
  
  
  RESULTS
  In overall population, statistically significant associations were not found between AVF malfunction and the genetic polymorphisms. In the male subgroup (n = 313), a single nucleotide polymorphism (SNP) of PRMT1, rs10415880 (IVS9-193 A/G), showed a significant association with AVF malfunction. Male patients with AA/AG genotype had inferior AVF outcomes compared to GG genotype, regarding primary patency (70.6% vs. 40.9%, p = 0.001), assisted primary patency (81.0% vs. 58.4%, p < 0.001) and secondary patency (83.7% vs. 63.3%, p < 0.001) at a 5-year observation period. From multivariate Cox regression model, the AA/AG genotypes of PRMT1 were an independent risk factor for AVF malfunction in men (HR: 4.539, 95% CI 2.015-10.223; p < 0.001). However, such associations were not found in women.
  
  
  CONCLUSIONS
  rs10415880, the SNP of PRMT1 could be a novel genetic marker associated with AVF malfunction risk in male HD patients. Those with AA and AG genotypes of rs10415880 may predict a poorer long-term patency of AVF.
authors.affiliation: a School of Medicine, National Yang-Ming University , Taipei , Taiwan ;|b Department of Medicine , Taipei Veterans General Hospital , Taipei , Taiwan ;|c Division of Nephrology , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Kuo-Hua
authors.initials: KH
authors.lastname: Lee
authors.affiliation: d Institute of Genome Sciences, National Yang-Ming University , Taipei , Taiwan ;|e Department of Medical Research , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Wen-Jung
authors.initials: WJ
authors.lastname: Tsai
authors.affiliation: a School of Medicine, National Yang-Ming University , Taipei , Taiwan ;|b Department of Medicine , Taipei Veterans General Hospital , Taipei , Taiwan ;|c Division of Nephrology , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chen
authors.affiliation: a School of Medicine, National Yang-Ming University , Taipei , Taiwan ;|b Department of Medicine , Taipei Veterans General Hospital , Taipei , Taiwan ;|c Division of Nephrology , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Wu-Chang
authors.initials: WC
authors.lastname: Yang
authors.affiliation: a School of Medicine, National Yang-Ming University , Taipei , Taiwan ;|f Division of Cardiovascular Surgery, Department of Surgery , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Chiu-Yang
authors.initials: CY
authors.lastname: Lee
authors.affiliation: a School of Medicine, National Yang-Ming University , Taipei , Taiwan ;|b Department of Medicine , Taipei Veterans General Hospital , Taipei , Taiwan ;|c Division of Nephrology , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Shuo-Ming
authors.initials: SM
authors.lastname: Ou
authors.affiliation: a School of Medicine, National Yang-Ming University , Taipei , Taiwan ;|g Division of Nephrology, Department of Medicine , Taipei City Hospital-Heping Branch , Taipei , Taiwan ;
authors.forename: Yung-Tai
authors.initials: YT
authors.lastname: Chen
authors.affiliation: h Department of Nephrology , Chi-Mei Medical Center , Tainan , Taiwan ;|i Department of Medical Research , Chi-Mei Medical Center , Tainan , Taiwan ;|j Department of Food Nutrition , Chung Hwa University of Medical Technology , Tainan , Taiwan.
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Chien
authors.affiliation: b Department of Medicine , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Pui-Ching
authors.initials: PC
authors.lastname: Lee
authors.affiliation: d Institute of Genome Sciences, National Yang-Ming University , Taipei , Taiwan ;|e Department of Medical Research , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Chung
authors.affiliation: a School of Medicine, National Yang-Ming University , Taipei , Taiwan ;|b Department of Medicine , Taipei Veterans General Hospital , Taipei , Taiwan ;|c Division of Nephrology , Taipei Veterans General Hospital , Taipei , Taiwan ;
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Lin
mesh_terms: D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000235:genetics*; D011110:Polymorphism, Genetic; D006435:Renal Dialysis; D012189:Retrospective Studies; D012737:Sex Factors; D013997:Time Factors
chemical_list: D009569:Nitric Oxide
keywords: Arteriovenous fistula (AVF); hemodialysis; nitric oxide; protein arginine methyltransferases1 (PRMT1); single nucleotide polymorphism (SNP)