Relevance Study On Associations Of VDR Gene Polymorphisms And Susceptibility To Lead Toxicity

Objective : Plumbism is still a puzzle of public health. Exposure to lead can lead to damage of mtiple organ and system. However, even with the same level of lead exposure, different individual display different symptom, it is possible that the genetic backgrounds of them is different. Vitamine D receptor is wide distributed in many tissues and cells, it's main biological effect is to influence the absorption and metabolism of calcium phosphorus. Because the metabolism of lead and calcium is very similar and influenced each other, we can infer by theoretically that VDR gene polymorphism can modify lead absorption . The purpose of present study is to confirm if VDR gene polymorphisms can modify lead metabolism and toxicity, and to investigate the reference dose of blood lead level and provide science ways to prevent worker health.Method : 112 male workers who had exposed to lead at least for one years were selected from a puddling factory in the suburb of Chengdu. 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. 112 blood and urine samples were collected , analyzing lead level in blood and urine ,δ-amino levulinic acid in urine , hemoglobin and blood calcium , An assay based on the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique of restriction enzyme .The relationship between VDR poly-morphisms and lead toxicity was studied by genotypes.Results: 1.VDR genotyping : Of the lead exposed worker analyzed for VDR genotypes, 99 (88.4%) were VDR-bb, 10 (8.9% ) were VDR -Bb , 3 (2.7%) were VDR-BB . The frequency of VDR-b and VDR-B were 0.929 and 0.071 respectively.2. The rational symptom of lead-exposured workers: The lead-exposured workers had some syndromes included acratia, limbs ache, memory descent, insomnia and dreams. The incidence rate of syndromes of VDR-bb genotype is mainly same as VDR -BB/Bb genotype , and the differe-nce was no significant.3. The systolic pressure, diastolic pressure, pulse and body mass index (BMI) of two genotypes were no significant, but the lower confidence limit on the benchmark dose (BMDL) of systolic pressure of VDR-BB/Bb genotype was lower that the BMDL of VDR-bb genotype.4. The blood lead level of VDR-Bb/BB genotype was higher than that VDR-bb genotype (P<0.05), the difference of urine lead and urine ALA level between two genotypes were no statistical significance , however the incidence coefficient of blood lead -urine lead ,blood lead - urine ALA of VDR-Bb/Bbgenotype was higher than VDR-bb genotype.5.The result of meta analysis is also show that the blood level of VDR-Bb/BBgenotype is higher than that of VDR-bb genotype (P<0.05 ) .6.The serum calcium level of VDR-Bb/BB genotype is lower than that ofVDR-bb genotype (P<0.05).7. The difference of hemoglobin levels of lead exposured workers betweenVDR-bb genotype and VDR-BB/Bb genotype was no statistical significance.The BMDL of hemoglobin of VDR-BB/Bb genotype was lower than that ofVDR-bb genotype. Conclusion : 1. The result of VDR genotyping was fitted with Hardy-Weinberg balance and also was same as others studies, but the difference between different nation and area was comparatively large.2. VDR-B allele may is one factor of the susceptible to lead, but may be many allele of VDR-B con-effect, so further study on multi-genes , multi-alleles is necessary.3. The multi-liner regression indicated the negative correlation between blood lead and serum calcium, blood lead and hemoglobin , and the coefficient correlation and BMDL of VDR-Bb/BB genotype were lower than those of VDR-bb genotype .these indicated the individual who have VDR-B allele is more susceptible to lead than those who have VDR-b allele only.4. The study of benchmark dose indicated the reference dose of lead is lower than exposure limit by law, and the benchmark dose of VDR-BB/Bb genotype is lower , then, this study indicated we should make exposure limit from molecular level.