EGFR and ORAI1 genetic polymorphisms associ-ate with serum TNF-alpha and blood lead levels among lead workers and controls

• Main Authors: Yi-Han Deng, 鄧伊涵
• Other Authors: Hung-Yi Chuang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/41350711049616584727

碩士 === 高雄醫學大學 === 公共衛生學研究所 === 101 === Background and Purpose: Lead are one of the most toxic heavy mentals.The mental lead is widely used in our life and in the industry.Popele may expose to lead not only in the job but also in the life.Exposed to lead is harmful various organs in human.Several lines of evidence have indicated that Pb is able to stimulate the expression of tumor of necrosis factor-alpha(TNF-α).Previous reports indicate that Pb2+ can entry into cells by activating mediators of inflammation vis the plasma membrane EGFR,and by store-operated Ca2+ channel(SOC).Thus,we investigate the association among EGFR/ORAI1(the key subunit of store-operated Ca2+ channel) gene polymorphisms,blood lead levels,and serum TNF-alpha. Materials and Methods: The present study included 426 lead-exposed subjects and controls in Taiwanese population.The questionnaire and blood sample collected information about demographic characteristics,biochemical data,blood lead levels,and serum TNF-α levels.DNA was also extracted for Genotyping. Genotyping was performed using TaqMan® SNP Genotyping Assays.The EGFR 3 SNPs (rs763317,rs2280653,rs2072454) and ORAI1 5 SNPs (rs712853,rs6486795,rs12313273,rs12320939,rs7135617) were genotyped in all subjects. Results: First,we divided blood lead levels into four groups (0≦BPb≦5, 5< BPb≦10, 10< BPb≦30 ,and BPb>30).After analysing,we found that serum TNF-α levels increased with blood lead levels.And then,using multiple regression analysis.After adjusting potential confounder,the association with blood lead levels and serum TNF-α levels was found.When blood lead levels increased 1μg/dL,serum TNF-α levels increased 0.34~0.38pg/mL.Two of ORAI1 SNPs(rs712853 and rs12313273)effected the lead-induced TNF-α expression. After adjusting blood lead levels and other confounder,the CT genotype of rs712853 polymorphism had significantly decreased the level of TNF-α 3.20(SE=1.39)pg/mL compared with the TT genotype. The CC genotype of rs712853 polymorphism had decreased the level of TNF-α 3.32(SE=2.15)pg/mL compared with the TT genotype.The CT genotype of rs12313273 had significantly increased the level of TNF-α 2.77(SE=1.36)pg/mL compared with the TT genotype. The CC genotype of rs12313273 polymorphism had increased the level of TNF-α 1.07(SE=2.18)pg/mL compared with the TT genotype.But all three EGFR SNPs were not. Conclusions: We showed that two of ORAI1 SNPs were associated with blood lead levels and serum TNF-α levels in Taiwanese population.