Introduction: Genetic variations are considered as internal contributors that play
a vital role in heavy metals metabolism. Aim of Work: to evaluate the impact of
metallothionine2A (MT2A) gene (rs10636 and rs28366003) single nucleotide
polymorphisms (SNPs) on the levels of blood heavy metals among exposed workers
in a copper smelters and detecting the genotypes associated with high levels of blood
metals. Materials and Methods: A cross-sectional analytical study was conducted
upon 65 exposed workers in a copper smelter at Helwan district and 65 non-exposed
personnel as a control group. Both groups were subjected to a detailed questionnaire
including age, duration of occupational exposure, smoking or other special habits,
present, past and family histories. General, local examinations and laboratory
investigations were done to determine blood levels of copper, lead and cadmium and
to estimate genetic polymorphism of Metallothionine2A (MT2A) gene (rs10636 and
rs28366003). Results: The GC genotype of rs10636 was the most prevalent genotype
among the exposed group while the genotype GG was most common among nonexposed.
As for rs28366003, we found GG was the most frequent genotype among the
exposed group but AG was the most prevalent among non-exposed group. Blood levels
of copper, lead and cadmium were highly elevated among the exposed group when
compared to non exposed especially among those who carried GC genotype of rs10636
SNPs. As regards rs28366003, a significantly high level of copper was seen among
subjects with GG genotype, but high levels of lead and cadmium were found with AA
and AG genotypes respectively. Duration of exposure, GC genotype of rs10636 and
GG of rs28366003 SNPs were significant predictors for high levels of copper, lead  and cadmium. Conclusion: Metallothionine2A (MT2A) isoform gene polymorphism is
associated with high levels of blood metals among exposed workers and it is considered
as an important internal contributor that predispose to metal toxicity.