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Background <p>Aluminum (Al) is the most abundant element in the Earth’s crust. Occupational exposure to aluminum can lead to serious adverse health effects for workers in the aluminum industry. Genetic variations could be considered as contributing internal factors for the susceptibility of individuals to toxicities related to Al exposure. Different experiments have investigated genetic polymorphism variations in metabolic pathways, which could significantly modulate an individual’s susceptibility to aluminum-induced toxicity. This study aimed to evaluate the effects of aluminum exposure on oxidant-antioxidant status, parathyroid hormone (PTH), and free testosterone levels. Also, to show whether an association exists between MTHFR A1298C (rs1801131) and CBS (844ins68) gene polymorphisms with the aforementioned biochemical parameters among occupationally exposed workers to Al.</p> Methods <p>Urinary heavy metals (Al, Cd, Ni, Cr, Pb) were measured through ICP-MS in 95 workers in the aluminum industry and 90 control individuals. We also analyzed serum MT-1, MDA, PTH, free testosterone, and TAC using ELISA methods. CBS (844ins68) and MTHFR A1298C gene polymorphisms were performed by (PCR-RFLP).</p> Results <p>Revealed a significant rise in serum MT-1, MDA, and urinary heavy metals levels with reductions in TAC, Free testosterone, and PTH levels. A negative relation was found between serum TAC, duration of exposure, and between age and serum free testosterone levels. In workers, the association of the wild type of MTHFR A1298C genotype with a rise in serum MT-1 and MDA levels and a decrease in TAC was observed compared to the control, while the heterozygote genotype AC was associated with reduced serum free testosterone, TAC, and PTH levels among the workers group. Moreover, serum MT-1 showed a significant rise in NN genotype of the CBS gene with a decline in serum TAC and PTH levels, while Heterozygote NI recorded reduced TAC levels among the worker group compared to the control. Significant reduction in serum TAC was shown in the heterozygote NI among the worker group compared to the control.</p> Conclusion <p>Association of wild-type and heterozygote genotype of both MTHFR A1298C (rs1801131) (AA and AC) and CBS (844ins68) (NN and NI) with reduced TAC levels among the worker group. Moreover, the AC genotype of MTHFR was associated with a decrease in the PTH and free testosterone levels among Al industry workers.</p>

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Genetic variation of CBS (844ins68) and MTHFR A1298C among aluminum-exposed workers with emphasis on the role of oxidative stress

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Nermeen S. A. Aziz,
  • Eman M. Shahy,
  • Mona M. Taha,
  • Heba Mahdy-Abdallah,
  • Khadiga S. Ibrahim,
  • Gehan M. Mahdy,
  • Lamia S. Ellaithy

摘要

Background

Aluminum (Al) is the most abundant element in the Earth’s crust. Occupational exposure to aluminum can lead to serious adverse health effects for workers in the aluminum industry. Genetic variations could be considered as contributing internal factors for the susceptibility of individuals to toxicities related to Al exposure. Different experiments have investigated genetic polymorphism variations in metabolic pathways, which could significantly modulate an individual’s susceptibility to aluminum-induced toxicity. This study aimed to evaluate the effects of aluminum exposure on oxidant-antioxidant status, parathyroid hormone (PTH), and free testosterone levels. Also, to show whether an association exists between MTHFR A1298C (rs1801131) and CBS (844ins68) gene polymorphisms with the aforementioned biochemical parameters among occupationally exposed workers to Al.

Methods

Urinary heavy metals (Al, Cd, Ni, Cr, Pb) were measured through ICP-MS in 95 workers in the aluminum industry and 90 control individuals. We also analyzed serum MT-1, MDA, PTH, free testosterone, and TAC using ELISA methods. CBS (844ins68) and MTHFR A1298C gene polymorphisms were performed by (PCR-RFLP).

Results

Revealed a significant rise in serum MT-1, MDA, and urinary heavy metals levels with reductions in TAC, Free testosterone, and PTH levels. A negative relation was found between serum TAC, duration of exposure, and between age and serum free testosterone levels. In workers, the association of the wild type of MTHFR A1298C genotype with a rise in serum MT-1 and MDA levels and a decrease in TAC was observed compared to the control, while the heterozygote genotype AC was associated with reduced serum free testosterone, TAC, and PTH levels among the workers group. Moreover, serum MT-1 showed a significant rise in NN genotype of the CBS gene with a decline in serum TAC and PTH levels, while Heterozygote NI recorded reduced TAC levels among the worker group compared to the control. Significant reduction in serum TAC was shown in the heterozygote NI among the worker group compared to the control.

Conclusion

Association of wild-type and heterozygote genotype of both MTHFR A1298C (rs1801131) (AA and AC) and CBS (844ins68) (NN and NI) with reduced TAC levels among the worker group. Moreover, the AC genotype of MTHFR was associated with a decrease in the PTH and free testosterone levels among Al industry workers.