Association of Genetic Polymorphisms of Renin-Angiotensin-Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients

Yu Wei Chen, Yu Te Wu, Jhin Shyaun Lin, Wu Chang Yang, Yung Ho Hsu, Kuo Hua Lee, Shou Ming Ou, Yung Tai Chen, Chia Jen Shih, Pui Ching Lee, Chia Hao Chan, Ming Yi Chung, Chih Ching Lin

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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.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume17
Issue number6
DOIs
Publication statusPublished - May 27 2016

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Keywords

  • angiotensin receptor gene
  • arteriovenous fistula
  • hemodialysis
  • single nucleotide polymorphism
  • thrombosis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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