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

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

doi:10.3390/ijms17060833

Open AccessArticle

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

by

Yu-Wei Chen

^1,2,3,4,†,

Yu-Te Wu

^3,4,†,

Jhin-Shyaun Lin

⁴,

Wu-Chang Yang

^3,4,

Yung-Ho Hsu

^1,2,

Kuo-Hua Lee

^3,4

,

Shou-Ming Ou

^3,4,

Yung-Tai Chen

⁵,

Chia-Jen Shih

⁶,

Pui-Ching Lee

⁷,

Chia-Hao Chan

^3,4,

Ming-Yi Chung

^8,9,*,‡ and

Chih-Ching Lin

^3,4,*,‡

¹

Division of Nephrology, Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, New Taipei 235, Taiwan

²

Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

³

Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan

⁴

School of Medicine, National Yang-Ming University, Taipei 112, Taiwan

⁵

Division of Nephrology, Department of Medicine, Taipei City Hospital, He-Ping Branch, Taipei 100, Taiwan

⁶

Division of Nephrology, Department of Medicine, Yuan-Shan Branch, Taipei Veterans General Hospital, I-Lan 264, Taiwan

⁷

Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan

⁸

Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan

⁹

Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work as first authors.

^‡

These authors contributed equally to this work as corresponding authors.

Int. J. Mol. Sci. 2016, 17(6), 833; https://doi.org/10.3390/ijms17060833

Submission received: 22 March 2016 / Revised: 14 May 2016 / Accepted: 18 May 2016 / Published: 27 May 2016

(This article belongs to the Special Issue Advances in Chronic Kidney Disease)

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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.

Keywords: hemodialysis; arteriovenous fistula; thrombosis; angiotensin receptor gene; single nucleotide polymorphism

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MDPI and ACS Style

Chen, Y.-W.; Wu, Y.-T.; Lin, J.-S.; Yang, W.-C.; Hsu, Y.-H.; Lee, K.-H.; Ou, S.-M.; Chen, Y.-T.; Shih, C.-J.; Lee, P.-C.; et al. Association of Genetic Polymorphisms of Renin–Angiotensin–Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients. Int. J. Mol. Sci. 2016, 17, 833. https://doi.org/10.3390/ijms17060833

AMA Style

Chen Y-W, Wu Y-T, Lin J-S, Yang W-C, Hsu Y-H, Lee K-H, Ou S-M, Chen Y-T, Shih C-J, Lee P-C, et al. Association of Genetic Polymorphisms of Renin–Angiotensin–Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients. International Journal of Molecular Sciences. 2016; 17(6):833. https://doi.org/10.3390/ijms17060833

Chicago/Turabian Style

Chen, Yu-Wei, 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, and et al. 2016. "Association of Genetic Polymorphisms of Renin–Angiotensin–Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients" International Journal of Molecular Sciences 17, no. 6: 833. https://doi.org/10.3390/ijms17060833

APA Style

Chen, Y.-W., Wu, Y.-T., Lin, J.-S., Yang, W.-C., Hsu, Y.-H., Lee, K.-H., Ou, S.-M., Chen, Y.-T., Shih, C.-J., Lee, P.-C., Chan, C.-H., Chung, M.-Y., & Lin, C.-C. (2016). Association of Genetic Polymorphisms of Renin–Angiotensin–Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients. International Journal of Molecular Sciences, 17(6), 833. https://doi.org/10.3390/ijms17060833

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

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