| Summary: | 碩士 === 高雄醫學大學 === 公共衛生學系職業安全衛生碩士班 === 103 === Background and objective:
Lead had neurotoxicity in peripheral sensory systems. Variant vitamin D receptor (VDR) genes and polymorphisms of Metallothioneins (MTs) were associated to lead toxicity. But no relationship between lead neurotoxicity and polymorphisms were discussed before. This study investigated the relationship among the polymorphisms of the VDR, MT1A, MT2A and lead toxicity to sensory nervous system in chronic lead – exposed workers
Methods:
We measured 181 workers’ vibration perception thresholds (VPT) and current perception thresholds (CPT) as neurological outcomes since 1990~1995. The outcome variables were then correlated to the subject’s index of long-term lead exposure that was calculated by the subject’s serial blood lead data in a period of working duration. The polymorphisms of VDR (Bsm rs1544410, Apa rs7975232 and Taq rs731236), MT1A (rs11640851 and rs8052394) and MT2A (rs10636 and rs28366003) are defined. The potential confounders, including age, gender, body height, smoking, alcohol consumption and working life span, were also collected and analyzed in linear regressions.
Results:
The regression coefficients of some gene polymorphisms were at lease 20 times larger than regression coefficients of TWICL. The regression analyses showed MT2A rs28366003(AG/AA) had significant different in all neurological outcomes except foot VPT and had the negative regression coefficients. All regression coefficients of TWICL mildly increased at the same time. MT1A rs11640851 (AA/CC) had significant difference in all neurological outcomes except hand and foot VPT. MT1A rs8052394 (GG/AA) had significant difference in hand and foot CPT 2000Hz. In MT2A rs10636, more C allele showed more influence in all three frequency of hand CPT. Among VDR, Apa rs7975232 (CC/AA) had most difference in all three frequency of hand CPT.
Conclusion:
TWICL needed to increase at lease 20μg/dL to have the same influence on neurotoxicity comparing with some different gene polymorphisms. Individuals with AG genotype for MT2A rs28366003 had neural protective effects by increasing sensitivity. CC genotype for Apa (rs7975232) of VDR and CC genotype for MT2A rs10636 increased the neurotoxicity on CPT more significant on hands. MT1A rs8052394 GG genotype has the protective effect on large myelinated nerve. MT1A rs11640851 AA genotype has susceptibilities to neurotoxicity. The interaction between zinc and lead to neurotoxicity needs further studies.
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