title: Association of Genetic Polymorphisms of Renin-Angiotensin-Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients.
abstract: Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001), lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025), right-sided (31.8% vs. 18.4%, p = 0.002) and upper arm AVF (26.6% vs. 9.7%, p < 0.001), and higher mean dynamic venous pressure (DVP) (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021). In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs), rs275653 (Odds ratio 1.90, p = 0.038) and rs1492099 (Odds ratio 2.29, p = 0.017) of angiotensin II receptor 1 (AGTR1), were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA) of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005). In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could be a potential genetic risk factor of AVF malfunction in male HD patients.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan. b101091063@tmu.edu.tw.|Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. b101091063@tmu.edu.tw.|Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. b101091063@tmu.edu.tw.|School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. b101091063@tmu.edu.tw.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. wyt0406@gmail.com.|School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. wyt0406@gmail.com.
authors.forename: Yu-Te
authors.initials: YT
authors.lastname: Wu
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. jhshlin0521@gmail.com.
authors.forename: Jhin-Shyaun
authors.initials: JS
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. wcyang@vghtpe.gov.tw.|School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. wcyang@vghtpe.gov.tw.
authors.forename: Wu-Chang
authors.initials: WC
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan. yhhsu@tmu.edu.tw.|Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. yhhsu@tmu.edu.tw.
authors.forename: Yung-Ho
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. dadabim3520@gmail.com.|School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. dadabim3520@gmail.com.
authors.forename: Kuo-Hua
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. okokyytt@gmail.com.|School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. okokyytt@gmail.com.
authors.forename: Shou-Ming
authors.initials: SM
authors.lastname: Ou
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei City Hospital, He-Ping Branch, Taipei 100, Taiwan. ytchen0117@gmail.com.
authors.forename: Yung-Tai
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, Yuan-Shan Branch, Taipei Veterans General Hospital, I-Lan 264, Taiwan. b001089010@tmu.edu.tw.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Shih
authors.affiliation: Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. pclee@vghtpe.gov.tw.
authors.forename: Pui-Ching
authors.initials: PC
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. box741029@yahoo.com.tw.|School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. box741029@yahoo.com.tw.
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Chan
authors.affiliation: Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan. lincc2@vghtpe.gov.tw.|Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan. lincc2@vghtpe.gov.tw.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Chung
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. mychung@ym.edu.tw.|School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. mychung@ym.edu.tw.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D001164:Arteriovenous Fistula / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D006435:Renal Dialysis / Q000379:methods; D012737:Sex Factors
chemical_list: C534931:AGT protein, human; C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: angiotensin receptor gene; arteriovenous fistula; hemodialysis; single nucleotide polymorphism; thrombosis