Abstract
Chronic exposure to lead is neurotoxic to the human peripheral sensory system. Variant vitamin D receptor (VDR) 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 VDR, MT1A, and MT2A 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 VDR, MT1A, and MT2A 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. MT1A rs11640851 (AA/CC) was associated with a statistically significant difference in all neurological outcomes except hand and foot VPT. MT1A rs8052394 was associated with statistically significant differences in hand and foot CPT 2000 Hz. In MT2A rs10636, those with the C allele showed a greater effect on hand CPT than those with the G allele. Among the VDR gene polymorphisms, the Apa rs7975232 (CC/AA) single nucleotide polymorphism was associated with the greatest difference in hand CPT. MT2A rs28366003 appeared to have a neural protective effect, whereas Apa (rs7975232) of VDR and MT2A rs10636 increased the neurotoxicity as measured by CPT in the hands. MT1A rs8052394 had a protective effect on large myelinated nerves. MT1A rs11640851 was associated with susceptibility to neurotoxicity.
Highlights
Lead is widely used in industry and remains a public health concern despite leaded gasoline being phased out in Taiwan in 2000 [1,2]
The aim of this study was to investigate the association of blood lead level, vibration perception thresholds (VPT), and current perception thresholds (CPT) in chronic occupational lead-exposed workers, and to assess whether the association was influenced by vitamin D receptor (VDR), MT1A, and MT2A
We found that MT1A rs8052394 GG type had protective effects in hand and foot CPT 2000 Hz compared to AA type
Summary
Lead is widely used in industry and remains a public health concern despite leaded gasoline being phased out in Taiwan in 2000 [1,2]. Recent epidemiological and toxicological studies have reported that lead exposure is associated with several diseases affecting the cardiovascular system [3] and renal system [4,5], as well as the hepatic system [6,7]. The blood lead levels in lead-exposed workers have been reported to be between 20 and 50 μg/dL in Taiwan [12]. Workers with 5 year mean blood lead levels greater than 30 μg/dL had higher vibration perception thresholds (VPTs) [13] than those who had lower blood lead levels. Using sensory nerve current perception thresholds (CPTs), we revealed that drinking milk (approximately 700 mL per day) might protect against lead peripheral neurotoxicity [14]
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