The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

Abstract

BackgroundBoth an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking.ObjectivesTo explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure.MethodsSeven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted.ResultsForty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin.ConclusionsNo C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally.

Research Article Human Serum Paraoxonase (PON-1) and hemochromatosis gene (HFE) gene polymorphisms in occupationally exposed lead workers from Saudi Arabia

“…Genetic variants in the HFE gene especially the C282Y variant and H63D variant play important roles in iron metabolism and hemochromatosis (Fan et al, 2014). Although not consistent with this study, a higher BLL was found in workers with H63D variant indicating that this genotype modifies the association of iron and lead irrespective of the C282Y allele.…”

“…HFE variant alleles may thus produce a modifying effect BLL toxicokinetics. Subjects with the H63D genotype showed an association between higher BLLs and elevated iron content indicating that carriers of this variant could be susceptible to lead poisoning (Fan et al, 2014). Interestingly studies in children indicated that the H63D and C282Y variants were significantly associated with elevated BLLs (Hopkins et al, 2008), although similar findings could not be reported in adults (Wright et al, 2004;Whitfield et al, 2007).…”

ECG conduction disturbances and ryanodine receptor expression levels in occupational lead exposure workers

“…Participants in our study were obtained as described previously 16. Briefly, all the subjects were staff members of a Pb smelter in Jiangxi province, China.…”

Hepcidin: SNP-Like Polymorphisms Present in Iron Metabolism and Clinical Complications of Iron Accumulation and Deficiency

“…HFE gene polymorphisms are associated with other clinical manifestations [52]. The H63D genotype modified the association between lead and iron metabolism, so that increased lead in the blood is associated with a higher iron content in the body or a lower concentration of transferrin, favouring lead poisoning [53]. The H63D polymorphism is attributed to a greater propensity to develop disorders in porphyrin metabolism, insulin resistance and diabetes development, as well as being associated with increased aggressiveness of hepatocarcinoma and pancreatic cancer [54,55].…”