title: Renin-angiotensin-aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease.
abstract: 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/C 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.
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Department of Chinese Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Horng-Sheng
authors.initials: HS
authors.lastname: Shiue
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tzen-Wen
authors.initials: TW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, New Taipei, Taiwan.
authors.forename: Yuh-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, New Taipei, Taiwan; Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Lin
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Bor-Cheng
authors.initials: BC
authors.lastname: Han
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: ymhsueh@tmu.edu.tw.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Hsueh
mesh_terms: D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D001151:Arsenic / Q000009:adverse effects / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000235:genetics* / Q000652:urine*; D012084:Renin-Angiotensin System / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013054:Spectrophotometry, Atomic; D013624:Taiwan
chemical_list: C534931:AGT protein, human; C544065:AGTR1 protein, human; D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D019405:Cytochrome P-450 CYP11B2; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D001151:Arsenic
keywords: Aldosterone synthase (CYP11B2); Angiotensinogen (AGT); Arsenic; Chronic kidney disease; Gene polymorphisms; Renin–angiotensin–aldosterone system