Genetic polymorphism of divalent metal transporter 1 gene intronic IVS4+44C/A in cadmium exposed population

Sittiporn Parnmen,Nattakarn Nooron, Pornpanna Chonnakijkul,Sujitra Sikaphan, Dutsadee Polputpisatkul, Chutimon Uttawichai, Rungsaeng Chankunasuka, Sriprapa Phatsarapongkul, Chidkamon Thunkhamrak, Unchalee Nitma, Nisakorn Palakul, Archawin Rojanawiwat

Research Square (Research Square)(2023)

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摘要
Abstract Background Exposure to cadmium is associated with a wide range of diseases, often influenced by genetic polymorphisms. This study aimed to investigate the role of the divalent metal transporter 1 ( DMT1 ) gene intronic IVS4 + 44C/A polymorphism in individuals aged 35–60 residing in cadmium-contaminated areas. Methods Blood samples were collected from 306 genetically unrelated individuals (158 females and 148 males). Urinary cadmium levels were measured as an indicator of cadmium exposure. Genotype frequencies were determined for the DMT1 IVS4 + 44C/A polymorphism. Results The geometric mean of urinary cadmium levels was significantly higher in females (4.03±4.15 µg/g creatinine) compared to males (2.62±2.73 µg/g creatinine). Remarkably, 85% of females and 66% of males exceeded the reference values for urinary cadmium concentration set by the German Human Biomonitoring (HBM) Commission (HBM I and II). Genotype frequencies were 65.4% homozygote typical (CC), 31.0% heterozygote (CA), and 3.6% homozygote atypical (AA). The C allele frequency was 80.9%, while the A allele frequency was 19.1%. Notably, the DMT1 IVS4 + 44C/A polymorphism significantly influenced urinary cadmium levels, with the CA genotype showing higher levels compared to CC and AA genotypes. Urinary cadmium levels were also statistically increased with the presence of the A allele (A + = CA + AA) compared to its absence (A − = CC). Furthermore, the CC genotype was associated with the highest number of individuals exceeding urinary cadmium reference values for HBM I and II across all age groups. Conclusions This study indicates that the CA genotype may signify susceptibility to prolonged cadmium exposure, given its association with elevated urinary cadmium levels. Additional research is essential for a thorough grasp of the implications of DMT1 gene polymorphisms on health outcomes, and to establish monitoring measures for populations residing in cadmium-contaminated areas.
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cadmium,divalent metal transporter,genetic polymorphism
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