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Delta-aminolevulinic acid dehydratase polymorphism and risk of brain tumors in adults.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Environmental Health Perspectives (Impact Factor: 7.03). 10/2005; 113(9):1209-11.
Source: PubMed

ABSTRACT The enzyme delta-aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme synthesis, can be inhibited by several chemicals, including lead, a potential risk factor for brain tumors, particularly meningioma. In this study we examined whether the ALAD G177C polymorphism in the gene coding for ALAD is associated with risk of intracranial tumors of the brain and nervous system. We use data from a case-control study with 782 incident brain tumor cases and 799 controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to the hospital. Blood samples were drawn and DNA subsequently sent for genotyping for 73% of subjects. ALAD genotype was determined for 94% of these samples (355 glioma, 151 meningioma, 67 acoustic neuroma, and 505 controls). Having one or more copy of the ALAD2 allele was associated with increased risk for meningioma [odds ratio (OR) = 1.6; 95% confidence interval (CI), 1.0-2.6], with the association appearing stronger in males (OR = 3.5; 95% CI, 1.3-9.2) than in females (OR = 1.2; 95% CI, 0.7-2.2). No increased risk associated with the ALAD2 variant was observed for glioma or acoustic neuroma. These findings suggest that the ALAD2 allele may increase genetic susceptibility to meningioma.

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    ABSTRACT: delta-aminolevulinic acid dehydratase (ALAD) catalyzes the second step of heme synthesis. The ALAD gene shows a polymorphism leading to 2 alleles (ALAD1 and ALAD2) and 3 phenotypes (ALAD 1-1, ALAD 1-2 and ALAD 2-2). This polymorphism has been shown to affect lead toxicity and the risk of meningioma. In addition, there is little evidence showing interethnic differences in the distribution of this polymorphism, especially in heterogeneous populations such as the Chinese population. We examined the distribution of genetic variants of the ALAD polymorphism in Han and Kazak Chinese. 938 unrelated Han and 1032 unrelated Kazak individuals were taken into the studies. Genomic DNA was extracted from venous blood and the genotypes for the ALAD polymorphism were determined by polymerase chain reaction followed by restriction fragment length polymorphism digestion and gel electrophoresis. We found a notable interethnic disparity in the distribution of ALAD genotypes and alleles. The ALAD2 allele was more common in Kazak than in Han (P
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    ABSTRACT: delta-Aminolevulinic acid dehydratase (ALAD) catalyzes the second step of heme synthesis. The ALAD gene shows a polymorphism leading to 2 alleles (ALAD1 and ALAD2) and 3 phenotypes (ALAD 1-1, ALAD 1-2 and ALAD 2-2). This polymorphism has been shown to affect lead toxicity and the risk of meningioma. In addition, there is little evidence showing interethnic differences in the distribution of this polymorphism, especially in heterogeneous populations such as the Chinese population. We examined the distribution of genetic variants of the ALAD polymorphism in Uighur and Yi Chinese. 1070 unrelated Uighur and 720 unrelated Yi individuals were taken into the studies. Genomic DNA was extracted from venous blood and the genotypes for the ALAD polymorphism were determined by polymerase chain reaction followed by restriction fragment length polymorphism digestion and gel electrophoresis. We found a notable interethnic disparity in the distribution of ALAD genotypes and alleles. The ALAD2 allele was more common in Uighur than in Yi (P <0.05). Correspondingly, the heterozygote (ALAD 1-2) or homozygote variant (ALAD 2-2) genotypes for this polymorphism were more common in Uighur than in Yi (P <0.05). The significant interethnic differences in the distribution of ALAD variants are found between the Uighur and Yi population. These findings may help us understand the interethnic disparities in susceptibility to lead toxicity and brain tumors.
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