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Title: Renin–angiotensin–aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease

A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin–angiotensin–aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruited from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[− 20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[− 344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96–2.01), of CKD; while those with the AGT(A[− 20]C) CC genotype had an inverse OR of CKD (0.20 (0.05–0.81)), and a high-risk genotype was defined as A/A + A/Cmore » for AGT(A[− 20C]) and T/T for CYP11B2(C[− 344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status. - Highlights: • AGT(− 20 C) and CYP11B2(− 344 T) genotypes were significantly associated with CKD. • Combined effect of high-risk genotypes and high urinary total arsenic on OR of CKD. • Combined effect on the CKD was modified by the hypertension and diabetes status.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [5] ;  [7] ;  [8] ;  [5] ;  [5] ;  [1] ;  [1] ;  [5]
  1. School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)
  2. Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)
  3. Department of Chinese Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan (China)
  4. Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China)
  5. (China)
  6. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)
  7. Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China)
  8. Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, New Taipei, Taiwan (China)
Publication Date:
OSTI Identifier:
22439808
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 279; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABSORPTION SPECTROSCOPY; ALDOSTERONE; ANGIOTENSIN; ARSENIC; CONCENTRATION RATIO; GENES; GENOTYPE; HAZARDS; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; HOSPITALS; HYDRIDES; HYPERTENSION; KIDNEYS; PATIENTS; POLYMERASE CHAIN REACTION; RECEPTORS; RENIN