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A polymorphism in metallothionein 1A (MT1A) is associated with cadmium-related excretion of urinary beta 2-microglobulin

Lei, Lijian; Chang, Xiuli; Rentschler, Gerda LU ; Tian, Liting; Zhu, Guoying; Chen, Xiao; Jin, Taiyi and Broberg Palmgren, Karin LU (2012) In Toxicology and Applied Pharmacology 265(3). p.373-379
Abstract
Objectives: Cadmium (Cd) toxicity of the kidney varies between individuals despite similar exposure levels. In humans Cd is mainly bound to metallothioneins (MT), which scavenge its toxic effects. Here we analyzed whether polymorphisms in MT genes MTIA and MT2A influence Cd-related kidney damage. Methods: In a cross-sectional study N = 512 volunteers were selected from three areas in South-Eastern China, which to varying degree were Cd-polluted from a smelter (control area [median Cd in urine U-Cd = 2.67 mu g/L], moderately [U-Cd = 423 mu g/L] and highly [U-Cd = 9.13 mu g/L] polluted areas). U-Cd and blood Cd (B-Cd) concentrations were measured by graphite-furnace atomic absorption spectrometry. MTIA rs11076161 (G/A), M72A rs10636 (G/C)... (More)
Objectives: Cadmium (Cd) toxicity of the kidney varies between individuals despite similar exposure levels. In humans Cd is mainly bound to metallothioneins (MT), which scavenge its toxic effects. Here we analyzed whether polymorphisms in MT genes MTIA and MT2A influence Cd-related kidney damage. Methods: In a cross-sectional study N = 512 volunteers were selected from three areas in South-Eastern China, which to varying degree were Cd-polluted from a smelter (control area [median Cd in urine U-Cd = 2.67 mu g/L], moderately [U-Cd = 423 mu g/L] and highly [U-Cd = 9.13 mu g/L] polluted areas). U-Cd and blood Cd (B-Cd) concentrations were measured by graphite-furnace atomic absorption spectrometry. MTIA rs11076161 (G/A), M72A rs10636 (G/C) and M72A rs28366003 (A/G) were determined by Taqman assays; urinary N-Acetyl-beta-(D)-Glucosaminidase (UNAG) by spectrometry, and urinary beta 2-microglobulin (UB2M) by ELISA. Results: Higher B-Cd (natural log-transformed) with increasing number of MTIA rs11076161 A-alleles was found in the highly polluted group (p-value trend = 0.033; all p-values adjusted for age, sex, and smoking). In a linear model a significant interaction between rs11076161 genotype and B-Cd was found for UNAG (p = 0.001) and UB2M concentrations (p = 0.001). Carriers of the rs11076161 AA genotype showed steeper slopes for the associations between Cd in blood and natural log-transformed UB2M (beta = 12, 95% CI 0.72-1.6) compared to GG carriers (beta = 030, 95% CI 0.15-0.45). Also for UNAG (natural log-transformed) carriers of the AA genotype had steeper slopes (beta = 0.55, 95% CI 027-0.84) compared to GG carriers (beta = 0.018, 95% CI - 0.79-0.11). Conclusions: MT1A rs11076161 was associated with B-Cd concentrations and Cd-induced kidney toxicity at high exposure levels. (C) 2012 Elsevier Inc. All rights reserved. (Less)
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author
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type
Contribution to journal
publication status
published
subject
keywords
Beta 2-microglobulin, Metallothionein, Genetic polymorphism, Kidney, Proteinuria
in
Toxicology and Applied Pharmacology
volume
265
issue
3
pages
373 - 379
publisher
Academic Press
external identifiers
  • wos:000312610500012
  • scopus:84870291620
ISSN
1096-0333
DOI
10.1016/j.taap.2012.09.006
language
English
LU publication?
yes
id
d82e021a-bb8f-4ead-ace4-de0b340e7eba (old id 3512146)
date added to LUP
2013-03-01 07:52:10
date last changed
2017-06-25 04:03:49
@article{d82e021a-bb8f-4ead-ace4-de0b340e7eba,
  abstract     = {Objectives: Cadmium (Cd) toxicity of the kidney varies between individuals despite similar exposure levels. In humans Cd is mainly bound to metallothioneins (MT), which scavenge its toxic effects. Here we analyzed whether polymorphisms in MT genes MTIA and MT2A influence Cd-related kidney damage. Methods: In a cross-sectional study N = 512 volunteers were selected from three areas in South-Eastern China, which to varying degree were Cd-polluted from a smelter (control area [median Cd in urine U-Cd = 2.67 mu g/L], moderately [U-Cd = 423 mu g/L] and highly [U-Cd = 9.13 mu g/L] polluted areas). U-Cd and blood Cd (B-Cd) concentrations were measured by graphite-furnace atomic absorption spectrometry. MTIA rs11076161 (G/A), M72A rs10636 (G/C) and M72A rs28366003 (A/G) were determined by Taqman assays; urinary N-Acetyl-beta-(D)-Glucosaminidase (UNAG) by spectrometry, and urinary beta 2-microglobulin (UB2M) by ELISA. Results: Higher B-Cd (natural log-transformed) with increasing number of MTIA rs11076161 A-alleles was found in the highly polluted group (p-value trend = 0.033; all p-values adjusted for age, sex, and smoking). In a linear model a significant interaction between rs11076161 genotype and B-Cd was found for UNAG (p = 0.001) and UB2M concentrations (p = 0.001). Carriers of the rs11076161 AA genotype showed steeper slopes for the associations between Cd in blood and natural log-transformed UB2M (beta = 12, 95% CI 0.72-1.6) compared to GG carriers (beta = 030, 95% CI 0.15-0.45). Also for UNAG (natural log-transformed) carriers of the AA genotype had steeper slopes (beta = 0.55, 95% CI 027-0.84) compared to GG carriers (beta = 0.018, 95% CI - 0.79-0.11). Conclusions: MT1A rs11076161 was associated with B-Cd concentrations and Cd-induced kidney toxicity at high exposure levels. (C) 2012 Elsevier Inc. All rights reserved.},
  author       = {Lei, Lijian and Chang, Xiuli and Rentschler, Gerda and Tian, Liting and Zhu, Guoying and Chen, Xiao and Jin, Taiyi and Broberg Palmgren, Karin},
  issn         = {1096-0333},
  keyword      = {Beta 2-microglobulin,Metallothionein,Genetic polymorphism,Kidney,Proteinuria},
  language     = {eng},
  number       = {3},
  pages        = {373--379},
  publisher    = {Academic Press},
  series       = {Toxicology and Applied Pharmacology},
  title        = {A polymorphism in metallothionein 1A (MT1A) is associated with cadmium-related excretion of urinary beta 2-microglobulin},
  url          = {http://dx.doi.org/10.1016/j.taap.2012.09.006},
  volume       = {265},
  year         = {2012},
}