Abstract
Metallothionein (MT) is a protein with function of heavy metal detoxification. However, studies about how single nucleotide polymorphisms (SNPs) of MT genes influence lead nephropathy are relatively scarce. Therefore, our aim is to investigate the association between blood lead levels and renal biomarkers and to study whether this association is influenced by the combination of MT1A and MT2A SNPs. Blood lead, urinary uric acid (UA), and urinary N-acetyl-beta-d-glucosaminidase (NAG) levels were analyzed from 485 participants. Genotyping were performed on MT1A SNPs (rs11640851 and rs8052394) and MT2A SNPs (rs10636 and rs28366003). The combined MT1A 2A SNPs were divided into 16 groups. Among renal biomarkers, urinary UA was negatively significant associated with the time-weighted index of cumulative blood lead (TWICL), while urinary NAG was positively significant with TWICL. Furthermore, the association between urinary UA and TWICL was significantly modified by group 6 of combined SNPs (MT1A 2 A SNPs combination were AAAGGGAA, ACAGGGAA, and ACGGGGAA). In conclusion, the negative association of urinary UA and TWICL is modified by group 6, which means participants of group 6 are more susceptible to lead nephrotoxicity.
Highlights
Metallothioneins (MTs) are high cysteine-containing, low molecular weight proteins that were initially found in the equine renal cortex in 195713
Our aim is to investigate the association of blood lead levels and renal biomarkers in chronic occupational lead exposure and to study whether the association was affected by combinations of MT1A and MT2A polymorphisms
The same principle of classification was applied in MT1A rs8052394, MT2A rs10636 and rs28366003, which were regarded rs8052394 AA, rs10636 GG and rs28366003 AA as wild types, respectively, all wild types combination belonged to group 1, the pure wild-type genetic carriers (CCAAGGAA), 20 participants as reference
Summary
Metallothioneins (MTs) are high cysteine-containing, low molecular weight proteins that were initially found in the equine renal cortex in 195713. The functions of these proteins include the maintenance of metal equilibria that protect against heavy metal ion toxicity and oxidative damage[14,15,16,17,18]. There are scarce investigations about the influence of MT1A and 2 A polymorphisms on renal function in chronic occupational lead exposure. Our aim is to investigate the association of blood lead levels and renal biomarkers in chronic occupational lead exposure and to study whether the association was affected by combinations of MT1A and MT2A polymorphisms
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