Kuo-Hua Lee1,2,3, Wen-Jung Tsai4,5, Yu-Wei Chen1,2,3, Wu-Chang Yang1,2,3, Chiu-Yang Lee1,6, Shuo-Ming Ou1,2,3, Yung-Tai Chen1,7, Chih-Chiang Chien8,9,10, Pui-Ching Lee2, Ming-Yi Chung4,5, Chih-Ching Lin1,2,3. 1. a School of Medicine, National Yang-Ming University , Taipei , Taiwan ; 2. b Department of Medicine , Taipei Veterans General Hospital , Taipei , Taiwan ; 3. c Division of Nephrology , Taipei Veterans General Hospital , Taipei , Taiwan ; 4. d Institute of Genome Sciences, National Yang-Ming University , Taipei , Taiwan ; 5. e Department of Medical Research , Taipei Veterans General Hospital , Taipei , Taiwan ; 6. f Division of Cardiovascular Surgery, Department of Surgery , Taipei Veterans General Hospital , Taipei , Taiwan ; 7. g Division of Nephrology, Department of Medicine , Taipei City Hospital-Heping Branch , Taipei , Taiwan ; 8. h Department of Nephrology , Chi-Mei Medical Center , Tainan , Taiwan ; 9. i Department of Medical Research , Chi-Mei Medical Center , Tainan , Taiwan ; 10. j Department of Food Nutrition , Chung Hwa University of Medical Technology , Tainan , Taiwan.
Abstract
OBJECTIVES: 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.
OBJECTIVES: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 HDpatients 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 HDpatients. Those with AA and AG genotypes of rs10415880 may predict a poorer long-term patency of AVF.
Entities:
Keywords:
Arteriovenous fistula (AVF); hemodialysis; nitric oxide; protein arginine methyltransferases1 (PRMT1); single nucleotide polymorphism (SNP)
Authors: Juliane Hannemann; Julia Zummack; Jonas Hillig; Leonard Rendant-Gantzberg; Rainer Böger Journal: J Clin Med Date: 2022-02-11 Impact factor: 4.241