title: Hypermethylations of RASAL1 and KLOTHO is associated with renal dysfunction in a Chinese population environmentally exposed to cadmium.
abstract: Exposure to cadmium (Cd) can affect both DNA methylation and renal function, but there are few examples of the association between epigenetic markers and Cd-induced kidney damage. It has been suggested that hypermethylation of the genes RASAL1 and KLOTHO is associated with renal fibrogenesis. To investigate whether hypermethylation of RASAL1 and KLOTHO in peripheral blood DNA can be associated with Cd exposure and/or Cd-induced renal dysfunction, the degrees of methylation of RASAL1 and KLOTHO in peripheral blood DNA from 81 residents in Cd-polluted and non-polluted areas were measured using bisulfate-PCR-pyrosequencing. Changes in blood cadmium (BCd), urinary cadmium (UCd), and kidney parameters were measured, and the glomerular filtration rate (eGFR) was estimated. The levels of BCd and UCd correlated positively with the levels of DNA methylation in RASAL1 and in KLOTHO. The more heavily exposed residents (BCd, 4.23-13.22μg/L; UCd, 8.65-32.90μg/g creatinine) exhibited obvious renal dysfunction. Notably, when Cd concentration in blood and urine was adjusted, the increased methylation level in RASAL1 was inversely correlated with eGFR (P<0.01) but the relationship between hypermethylation of KLOTHO and eGFR was not statistically significant. The methylation of RASAL1 increased along with the increased abnormal prevalence of eGFR. Our findings suggest that Cd exposure can induce the hypermethylation of RASAL1 and KLOTHO. Hypermethylation of RASAL1 may be an indicator of the progress for chronic kidney disease.
authors.affiliation: School of Public Health, Fudan University, 130 DongAn Road, Shanghai 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Yihuai
authors.initials: Y
authors.lastname: Liang
authors.forename: Lijian
authors.initials: L
authors.lastname: Lei
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhu
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Taiyi
authors.initials: T
authors.lastname: Jin
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
mesh_terms: D044466:Asian People; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D002681:China; D019175:DNA Methylation / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects; D044127:Epigenesis, Genetic; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D051437:Renal Insufficiency / Q000209:etiology* / Q000503:physiopathology
chemical_list: D020690:GTPase-Activating Proteins; C580923:RASAL1 protein, human; D002104:Cadmium; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Alb; B2M; BCd; Cadmium; Cd; Hypermethylation; KLOTHO; N-acetyl-β-d-glucosaminidase; NAG; Pyrosequencing; RASAL1; Renal dysfunction; Scr; UCd; albumin; blood cadmium; cadmium; eGFR; estimated glomerular filtration rate; serum creatinine; urinary cadmium; β(2)-microglobulin