171 The association of blood lead level and renal effects may be modified by metallothionein 1a 2a polymorphisms

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Abstract

Introduction

Lead toxicity plays an important role in public health. It causes multiple organs damage, and nephrotoxicity is included. Metallothionein (MT) is a cysteine-rich, low molecular weight protein with function of heavy metal detoxification. However, study about how the MT1A and MT2A single nucleotide polymorphisms (SNPs) influence the lead nephropathy is relatively scarce. Our aim is to investigate the association of blood lead levels and renal biomarkers in chronic lead exposure, and to study whether the association was influenced by MT1A2A SNPs.

Methods

Blood samples were collected from 485 participants during their annual health examination after informed consent letters were obtained. The blood lead level,urinary creatinine, urinary uric acid, and urinary N-acetyl-beta-d-glucosaminidase (NAG) were measured and analysed. DNA was extracted and used for real-time PCRgenotyping two MT1A SNPs (rs11640851 and rs8052394) and two MT2A SNPs (rs10636 and rs28366003). The MT1A2A SNPs combination was dividedinto 16 groups. Data were treated for descriptive analysis, one-way ANOVA, and multiple linear regressions by SPSS.

Results

Urine uric acid had significantly negative association with time-weighted index of cumulative blood lead (TWICL) after adjusting other potential confounders except 16 groups of MT1A2A SNPs combination. Moreover, the association was modified by 16 groups of SNPs combination. For urine uric acid, group 6th and group 12th were more susceptible to lead toxicity, while group 5th was lesssusceptible to lead toxicity. On the other hand, urinary NAG was positively associated with TWICL no matter whether the 16 groups were adjusted or not.

Conclusion

Urinary uric acid and urinary NAG might be considered as proper indicators of lead nephrotoxicity. Moreover, MT1A2A combination 16 groups were modifiers in the relationship between urinary uric acid and TWICL. The group 5th was positive association while group 6th and 12th were negative association with TWICL on urinary uric acid

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