Association Of Genetic Susceptibility To Lead Toxicity With Single Nucleotide Polymorphism In XRCC3 And XPD Genes

Objective:To investigate the distribution of XRCC3Thr241Met,XPDAsp312Asn and XPDLys751Gln polymorphisms in lead-exposed workers and its association with lead toxicity. To explore the impact of these XRCC3 and XPD polymorphisms on phenotypes including lead level in blood and urine,ZPP level in blood and self-conscious symptoms. Our work aimed at understanding the effects of XRCC3 and XPD gene polymorphisms on lead genetic susceptibility. Methods:326 male workers who had exposed to lead at least for one years were selected from a storage battery factory. Except those who had history of disease,such as hypertension,heart disease,diabetes,tumor and severe mental disorder.Questionnaire was adopted to investigate demographic information and syndromes of lead workers,and physical examinations were conducted to check health status.326 blood and urine samples were collected, analyzing lead level in blood and urine,ZPP level in blood,an assay based on the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)technique of restriction enzyrne. The participants were divided into different groups,that is XRCC3-241CC,XRCC3-241CT,XRCC3-241TT,XPD-312GG,XPD-312GA,XPD-312AA,XPD-751AA,XPD-751AC and XPD-751CC.The relationship between XRCC3 and XPD polymorphisms and lead toxicity was studied by genotypes.Results:1. The distribution frequencies of the alleles and genotypes of XRCC3Thr241Met,XPDAsp312Asn and XPDLys751Gln in 326 Lead-exposed workers were in agreement with the Hardy-Weinberg equilibrium (P>0.05).2. Two groups respectively(XRCC3-241CC/CT+TT,XPD-312GG/GA+AA,XPD-751AA/AC+CC)all had no significant difference in age,work age and lead job duration(P>0.05). The proportion of education, drinking,smoking ,exercising of the groups was no significant differene (P>0.05).3.the difference of urine lead and blood ZPP level between two groups respectively (XRCC3-241CC/CT+TT,XPD-312GG/GA+AA,XPD-751AA/AC+CC)were no statistical significance (P>0.05). The blood lead level of XRCC3-241CT+TT genotype was higher than that XRCC3-241CC genotype(P<0.05),However the difference of blood lead level between the groups respectivelyXPD-312GG/GA+AA and XPD-751AA/AC+CC were no statistical significance(P>0.05).4. The lead-exposed workers had some syndromes included acratia,insomnia,dreams and anorexia.The incidence rate of syndromes of XRCC3-241CT+TT genotype is higher than XRCC3-241CC (P<0.05) , and subjects with XRCC3-241CT+TT genotype had an increased risk of high blood lead(OR=2.34,95%CI=1.61～5.13),but the incidence rate of syndromes and high blood lead of XPD-312GG and XPD-751AA genotype were maminly same as XPD-312GA+AA and XPD-751AC+CC genotype respectively ,and the difference was no significant (P>0.05).5. The analysis of gene-gene interaction showed that there were no obvious interaction to XRCC3Thr241Met,XPDAsp312Asn and XPDLys751Gln (P>0.05).Conclusion: 1. The XRCC3Thr241Met polymorphisms and the blood lead level has revealed the connection,and the C→T polymorphisms increase the risks of lead toxicity for the lead-exposed workers ,and the XRCC3-241CT/TT genotype may is the susceptible genotype to lead toxicity.2.The XPDAsp312Asn,XPDLys751Gln polymorphisms may is not one factor of the susceptible to lead toxicity.3.There were no obvious interaction to XRCC3Thr241Met,XPDAsp312Asn and XPDLys751Gln.