, 2011). The G allele of MT2A rs10636 abolishes a binding site for DREAM, a calcium-regulated transcriptional repressor ( Carrion et al., 1999); and creates one for EKLF, which is involved in transcriptional regulation in erythroids
( Donze et al., 1995). The G allele of MT2A rs28366003 abolishes a binding site for MTF1, a transcription factor that is known to induce gene expression in response to Cd. The frequency of the rs11076161 A allele among Europeans (0.26) is estimated to be lower than in the Chinese population, whereas it is higher among Africans (0.52) (www.ncbi.nlm.nih/projects/SNP), suggesting that differences in susceptibility to renal toxicity between different populations could be expected. The finding of a relationship between B-Cd and MT1A rs11076161 makes it difficult to distinguish whether the genotype affects the Cd body burden, or if it has a specific effect
on Cd in blood. Genotype selleck products specific expression of MT1A caused by presence/absence of a ZBTB16 transcription signal could be the underlying mechanism that explains why AA/AG carriers are at higher risk to develop affected kidney function upon exposure to Cd. More studies will be needed to verify the effect of rs11076161 genotypes on Cd-induced renal toxicity. An ideal way would be to obtain cell lines that differ in rs11076161 genotype and study their cadmium sensitivity. NU7441 The MT2A rs28366003 genotype seemed to have a slight effect on the B-Cd levels, which was more evident in the low exposure group. However, when considering B-Cd in tertiles, there was no effect of this SNP on the Cd concentrations and we could not
support evidence from other studies. The variant genotype GG was associated with increased concentrations of Cd in the kidney tissue from autopsies ( Kayaalti et al., 2010 and Kita 17-DMAG (Alvespimycin) HCl et al., 2006) and blood ( Kayaalti et al., 2011). Kita et al. (2006) demonstrated a reduced expression of this G variant in response to Cd and Zn exposure, and thus, one could expect that G carriers would suffer more toxic effects of Cd. However, the latter could not be supported in our study. Rather the opposite was observed; G carriers had lower levels of UNAG in urine. In conclusion, this study identifies that the rs11076161 G → A exchange of MT1A influences the toxicity of Cd on renal function: AA genotype may be more sensitive to cadmium toxicity than those with the GG genotype. It suggests that MT1A variation may be an additional useful indicator to monitor for prediction of the risk of renal dysfunction in certain populations. The authors declare that they have no competing interests. This study was supported by the Swedish Council for Working Life and Social Research, and The European Union within the Sixth Framework Programme for RTD (“PHIME” contract no FOOD-CT-2006-016253.