Effects of Vitamin D Receptor, Metallothionein 1A, and 2A Gene Polymorphisms on Toxicity of the Peripheral Nervous System in Chronically Lead-Exposed Workers.

Chronic exposure to lead is neurotoxic to the human peripheral sensory system. Variant genes and polymorphisms of metallothioneins (MTs) are associated with different outcomes following lead toxicity. However, no evidence of a relationship between lead neurotoxicity and polymorphisms has previously been presented. In this study, we investigated the relationship between the polymorphisms of , , and genes and lead toxicity following chronic occupational lead exposure. We measured vibration perception thresholds (VPT) and current perception thresholds (CPT) in 181 workers annually for five years. The outcome variables were correlated to the subject's index of long-term lead exposure. Polymorphisms of , , and were defined. The potential confounders, including age, sex, height, smoking, alcohol consumption, and working life span, were also collected and analyzed using linear regression. The regression coefficients of some gene polymorphisms were at least 20 times larger than regression coefficients of time-weighted index of cumulative blood lead (TWICL) measures. All regression coefficients of TWICL increased slightly. rs11640851 (AA/CC) was associated with a statistically significant difference in all neurological outcomes except hand and foot VPT. rs8052394 was associated with statistically significant differences in hand and foot CPT 2000 Hz. In rs10636, those with the C allele showed a greater effect on hand CPT than those with the G allele. Among the gene polymorphisms, the Apa rs7975232 (CC/AA) single nucleotide polymorphism was associated with the greatest difference in hand CPT. rs28366003 appeared to have a neural protective effect, whereas Apa (rs7975232) of and rs10636 increased the neurotoxicity as measured by CPT in the hands. rs8052394 had a protective effect on large myelinated nerves. rs11640851 was associated with susceptibility to neurotoxicity.