Delta-aminolevulinic Acid Dehydratase Polymorphism Research Articles

Association of Delta-Aminolevulinic Acid Dehydratase Polymorphism with Blood Lead and Hemoglobin Level in Lead Exposed Workers

Association of Delta-Aminolevulinic Acid Dehydratase Polymorphism with Blood Lead and Hemoglobin Level in Lead Exposed Workers

Association between delta-aminolevulinic acid dehydratase polymorphism and placental lead levels.

Lead inhibits the delta-aminolevulinic acid dehydratase (ALAD) activity and results in neurotoxic aminolevulinic acid accumulation in the blood. During pregnancy, lead in the maternal blood can easily cross the placenta. The aim of this study was to determine whether the maternal ALAD G177C polymorphism (rs1800435) was related to the placental lead levels. The study population comprised 97 blood samples taken from mothers to investigate ALAD G177C polymorphism and their placentas to measure lead levels. ALAD G177C polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique and atomic absorption spectrometry (AAS) equipped with a graphite furnace and Zeeman background correction system was used for lead determination. The median placental lead levels for ALAD1-1, ALAD1-2 and ALAD2-2 genotypes were 7.54 μg/kg, 11.78 μg/kg and 18.53 μg/kg, respectively. Statistically significant association was found between the maternal ALAD G177C polymorphism and placental lead levels (p<0.05). This study suggested that maternal ALAD G177C polymorphism was associated with placental lead levels.

Investigation of delta-aminolevulinic acid dehydratase polymorphism affecting hematopoietic, hepatic and renal toxicity from lead in Han subjects of southwestern China

This study is to explore the effect of ALAD polymorphism on hematopoietic, hepatic and renal toxicity from lead in occupational exposure workers. We conducted a cross-sectional study on 156 workers with occupational exposure to lead between 2002 and 2007. The results of laboratory examinations were analyzed. The authors found that workers with the ALAD 1-1 genotype were associated with higher blood lead level than those with the ALADl-2 genotype. Blood and urine lead levels were much higher in storage battery workers than in cable workers. The urine ALA and blood ZPP levels in workers with the ALAD 1-1 genotype were higher than those with the ALADl-2 genotype. The serum Cr level in workers with the ALADl-1 genotype was much higher than those with the ALADl-2 genotype especially in higher lead exposure level. The ALAD-2 protein might modify the kinetics of lead in blood at a relatively higher blood lead level and protect against hematopoietic, hepatic and renal toxicity from lead. Urine ALA, blood ZPP and serum Cr levels might be considered as effective biological monitoring partners of lead induced hematopoietic and renal toxicology.

Effects of Delta-Aminolevulinic Acid Dehydratase Polymorphisms on Susceptibility to Lead in Han Subjects from Southwestern China

This study is to determine the distribution of the delta-aminolevulinic acid dehydratase (ALAD) polymorphism among Han subjects of the Chinese population and to study whether the polymorphism in the ALAD gene modifies the toxicity of lead in lead-exposed workers. For this purpose we conducted a cross-sectional study on 156 Chinese workers who were exposed to lead in lead-acid battery and electric-flex manufacturing plants. The authors found that the allele frequencies of ALAD1 and ALAD2 were 0.9679 and 0.0321, respectively. Workers with the ALAD 1-1 genotype were associated with higher blood lead levels than those with the ALAD 1-2 genotype. Blood and urine lead levels were much higher in storage battery workers than in cable workers. The self-conscious symptom survey showed that the incidences of debilitation, amnesia and dreaminess were much higher in those had more than five years of tenure or contact with lead on the job within the ALAD 1-1 genotype subgroup. Laboratory examinations showed that serum iron and zinc levels in workers’ with the ALAD 1-2 genotype were higher than those with the ALAD 1-1 genotype, especially in storage-battery workers. Correlation analysis indicated that the blood lead level negatively correlated with serum calcium, iron and zinc level. The data of this study suggest that the ALAD gene polymorphism and serum ion levels may modify the kinetics of lead in blood. Therefore, the authors recommend that an adequate intake of dietary calcium, iron, and zinc or the calcium, iron, and zinc supplementation should be prescribed to Chinese lead exposed workers.

Modifying Influence of the Delta-Aminolevulinic Acid Dehydratase Polymorphism on Lead in Bone, Erythrocytes, and Urine

ISEE-551 Objective: The delta-aminolevulinic acid dehydratase (ALAD) polymorphism has been shown in some studies to alter the impact of lead on kidney function and other health outcomes, which may be due to associated effects on lead binding and tissue distribution kinetics. We evaluated the modifying influence of the ALAD polymorphism on the interrelations between erythrocyte lead, urine lead, and bone lead, and ALAD interaction with bone and erythrocyte lead in association with plasma lead among older community-exposed men. Materials and Methods: Information on ALAD genotype, lead levels in blood, bone (measured using K-shell x-ray fluorescence), and urine were collected for 727 Normative Aging Study participants. We created a structural equation model (SEM) to simultaneously evaluate the association between erythrocyte lead (estimated from whole blood lead) and bone lead, and between urine lead with erythrocyte lead by ALAD genotype (1–2/2–2 vs. 1–1). A second SEM assessed the relation between a latent plasma lead covariate, using urine lead as a surrogate measure, and bone and erythrocyte lead among ALAD 1–2 and 1–1 carriers. Potential predictors of lead levels in urine, erythrocytes, and bone were included in the SEMs. Results: Of the 727 participants, 16% (113) were heterozygous (1–2) and 1% (7) were homozygous (2–2) for the ALAD-2 allele, respectively. Among both ALAD 1–2/2–2 and 1–1 carriers, patella bone lead was associated with higher erythrocyte lead (P<0.05). We observed significant associations between erythrocyte lead and higher urine lead (P<0.05), and between erythrocyte lead and higher plasma lead (P<0.05), respectively, which did not vary with respect to ALAD genotype. Conclusions: The results of this study do not provide evidence that the ALAD genotype modifies the association between erythrocyte lead and plasma lead. These findings should be confirmed in populations with different exposure profiles and account for potential temporal changes in the internal distribution of lead.

Lead and delta-aminolevulinic acid dehydratase polymorphism: where does it lead? A meta-analysis.

BackgroundLead poisoning affects many organs in the body. Lead inhibits δ-aminolevulinic acid dehydratase (ALAD), an enzyme with two co-dominantly expressed alleles, ALAD1 and ALAD2.ObjectiveOur meta-analysis studied the effects of the ALAD polymorphism on a) blood and bone lead levels and b) indicators of target organ toxicity.Data sourceWe included studies reporting one or more of the following by individuals with genotypes ALAD1-1 and ALAD1-2/2-2: blood lead level (BLL), tibia or trabecular lead level, zinc protoporphyrin (ZPP), hemoglobin, serum creatinine, blood urea nitrogen (BUN), dimercaptosuccinic acid–chelatable lead, or blood pressure.Data extractionSample sizes, means, and standard deviations were extracted for the genotype groups.Data synthesisThere was a statistically significant association between ALAD2 carriers and higher BLL in lead-exposed workers (weighted mean differences of 1.93 μg/dL). There was no association with ALAD carrier status among environmentally exposed adults with BLLs < 10 μg/dL. ALAD2 carriers were potentially protected against adverse hemapoietic effects (ZPP and hemoglobin levels), perhaps because of decreased lead bioavailability to heme pathway enzymes.ConclusionCarriers of the ALAD2 allele had higher BLLs than those who were ALAD1 homozygous and higher hemoglobin and lower ZPP, and the latter seems to be inversely related to BLL. Effects on other organs were not well delineated, partly because of the small number of subjects studied and potential modifications caused by other proteins in target tissues or by other polymorphic genes.

Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: the Normative Aging Study

Objective: To determine whether a polymorphism the in δ-aminolevulinic acid dehydratase (ALAD) gene modifies the neurotoxicity of lead in older adults. Methods: The authors studied men participating in the Department...