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Molecular Epidemiology Study On Associations Of VDR And ALAD Gene Polymorphisms And Susceptibility To Lead Toxicity

Posted on:2004-07-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:X B YeFull Text:PDF
GTID:1104360095962809Subject:Occupational and Environmental Health
Abstract/Summary:PDF Full Text Request
Lead has been a known toxicant for thousands of years and remains a persistent environmental health threat. Exposure to lead can result in significant multi-organ toxicity, with adverse health effects involving the nervous, hematological and reproductive systems. Chronic occupational exposure to lead, or consumption of illicit alcohol adulterated with lead, has also been linked to a high incidence of renal dysfunction, characterized by glomerular and tubulointerstitial changes resulting in chronic renal failure, hypertension, hyperuricemia and gout. It's difficult, however, to define safe level of lead exposure because adverse health effects can be observed among population with very low lead exposure. Workers in the same workplace can show different health risk of lead toxicity and poisoning. These phenomena may be explained by different nutrition, lifestyle and genetic background. So, the identification of genetic susceptibility is very important for prevention and control of lead exposure.A polymorphism in (-aminolevulinic acid dehydratase gene was identified in 1981.There are two alleles, ALAD-1 and ALAD-2, three genotypes of ALAD-11, ALAD-12 and ALAD-22. Several studies showed that population with ALAD-12/22 genotype had higher body lead levels. However, other studies didn't support these findings. Moreover, limitations of no cumulative lead exposure dose, no duplicate and bad control of confounders existed in some of these studies. Calcium and lead have similar process of metabolism and interact with each other. Dietary calcium intake can modify lead absorption. Some studies showed VDR BsmI polymorphism (VDR-bb, VDR-Bb and VDR-BB genotypes) was associated with calcium absorption, bone density and osteoporosis. So, it's expected that VDR BsmI polymorphism can modify lead absorption. More studies are needed to explore the effects of ALAD and VDR polymorphism on lead absorption, retention, excretion and toxicity. The purpose of present study is to confirm if ALAD and VDR gene polymorphisms can modify lead metabolism and toxicity.Two hundred and sixteen workers with occupational and environmental lead exposure from lead smelter factory and lead acid battery factory and 47 beer workers with environmental lead exposure were selected. Among these 263 subjects, 215 are males and 48 are females, with average age of 43.2 years. Five milliliter vein blood were collected with 1 ml for blood lead determination and 4ml for serum and blood clotting. Genomic DNA was isolated from blood clotting. Serum hormone levels of testosterone (T), luteinishing hormone (LH) and follicle stimulationg hormone (FSH) for 163 male workers with occupational lead exposure were measured by ELISA. Urine samples were collected for determination of albumin (ALB) concentration, N-acetyl-(-glucosaminidase(NAG) activity, urinary lead(UPb) and (-aminolevulinic acid levels(UALA), creatinine level(Cr). All urinary parameters were adjusted by creatinine. Blood hemoglobin (Hb) level and blood pressure were measured. Forty-one workers with urinary lead level more than 0.08mg/L were treated by oral 2,3-dimercaptosuccinic acid. Urinary chelatable lead (DMSA-Pb) levels were measured for these 41 workers. Questionnaire was used to collect basic information, information of smoking, alcohol consumption and occupational history. Cumulative lead exposure levels were estimated for each subject. Meta analysis method was employed to evaluate effects of VDR and ALAD gene polymorphisms on blood lead levels. Using BMDS program compared dose-response relationships between different ALAD and VDR genotypes.Present study showed that the frequencies for ALAD-11 and ALAD-12 genotype were 93.2% and 6.8% respectively. No ALAD-12 genotype was found. Frequencies of alleles of ALAD-1 and ALAD-2 are 96.6% and 3.4% respectively. Subjects with VDR-bb, VDR-Bb and VDR-BB genotypes occupied 90.1%,7.6% and 2.3% of current study population, with frequencies of 93.9% for VDR-b allele and 6.1% for VDR-B allele.Beer workers with ALAD-12 genotype had lower blood lead lev...
Keywords/Search Tags:Susceptibility
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