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Association between ?-aminolevulinate dehydratase G177C polymorphism and blood lead levels in brain tumor patients.

ABSTRACT: As the ?-aminolevulinic acid dehydratase (ALAD) G177C polymorphism affects the toxicokinetics of lead in the body, and the corresponding exposure to lead may increase the risk of adult brain tumors, we hypothesize that there is a possible association of the ALAD G177C genotype and the risk of brain tumors in human. Therefore, the aim of the present study was to clarify the role of the ALAD enzyme gene polymorphism at position G177C in the pathogenesis of brain tumors and its correlation to lead exposure. The ALAD gene polymorphism at position G177C was genotyped using the polymerase chain reaction with restriction fragment length polymorphism method and measured the blood lead level by atomic absorption in 81 brain tumor patients and compared the results with 81 controls. The frequency of the GC genotype (ALAD1-2) was significantly increased in primary brain tumor patients compared to the control group. The genotype frequency of ALAD2 (ALAD1-2 and ALAD2-2) was significantly higher in the meningioma patients but was not significant in glioma patients. There was no significant difference in the number of patients and blood lead level when compared with the control. There was a significant increase when compared to ALAD1 regarding a mean value of the lead level. The genotyping of the ALAD G177C polymorphism in the present study revealed a significant association between ALAD2 and brain tumors. The ALAD G177C polymorphism may modify the lead kinetics in the blood, is associated with higher blood lead burden and may provide a biomarker of neurotoxic risk.

SUBMITTER: Taha MM

PROVIDER: S-EPMC4535054 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Association between δ-aminolevulinate dehydratase G177C polymorphism and blood lead levels in brain tumor patients.

Taha Mahmoud Mostafa MM Gaber Osama Abd El Aziz OA Sabbah Norhan Abdalla NA Abd Elazem Abd Allah S AA

Molecular and clinical oncology 20150625 5

As the δ-aminolevulinic acid dehydratase (<i>ALAD</i>) G177C polymorphism affects the toxicokinetics of lead in the body, and the corresponding exposure to lead may increase the risk of adult brain tumors, we hypothesize that there is a possible association of the <i>ALAD</i> G177C genotype and the risk of brain tumors in human. Therefore, the aim of the present study was to clarify the role of the ALAD enzyme gene polymorphism at position G177C in the pathogenesis of brain tumors and its correl ...[more]

PMID: 26623039

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Project description:ImportanceLead is a neurotoxin with well-documented effects on health. Research suggests that lead may be associated with criminal behavior. This association is difficult to disentangle from low socioeconomic status, a factor in both lead exposure and criminal offending.ObjectiveTo test the hypothesis that a higher childhood blood lead level (BLL) is associated with greater risk of criminal conviction, recidivism (repeat conviction), conviction for violent offenses, and variety of self-reported criminal offending in a setting where BLL was not associated with low socioeconomic status.Design, setting, and participantsA total of 553 individuals participated in a prospective study based on a population-representative cohort born between April 1, 1972, and March 31, 1973, from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (December 2012). Statistical analysis was performed from November 10, 2016, to September 5, 2017.ExposuresBlood lead level measured at age 11 years.Main outcomes and measuresOfficial criminal conviction cumulative to age 38 years (data collected in 2013), single conviction or recidivism, conviction for nonviolent or violent crime, and self-reported variety of crime types at ages 15, 18, 21, 26, 32, and 38 years.ResultsParticipants included 553 individuals (255 female and 298 male participants) who had their blood tested for lead at age 11 years. The mean (SD) BLL at age 11 years was 11.01 (4.62) μg/dL. A total of 154 participants (27.8%) had a criminal conviction, 86 (15.6%) had recidivated, and 53 (9.6%) had a violent offense conviction. Variety scores for self-reported offending ranged from 0 to 10 offense types at each assessment; higher numbers indicated greater crime involvement. Self-reported offending followed the well-established age-crime curve (ie, the mean [SD] variety of self-reported offending increased from 1.99 [2.82] at age 15 years to its peak of 4.24 [3.15] at age 18 years and 4.22 [3.02] at age 21 years and declined thereafter to 1.10 [1.59] at age 38 years). Blood lead level was a poor discriminator between no conviction and conviction (area under the curve, 0.58). Overall, associations between BLL and conviction outcomes were weak. The estimated effect of BLL was lower for recidivism than for single convictions and lower for violent offending than for nonviolent offending. Sex-adjusted associations between BLL reached statistical significance for only 1 of the 6 self-reported offending outcomes at age 15 years (r = 0.10; 95% CI, 0.01-0.18; P = .02).Conclusions and relevanceThis study overcomes past limitations of studies of BLL and crime by studying the association in a place and time where the correlation was not confounded by childhood socioeconomic status. Findings failed to support a dose-response association between BLL and consequential criminal offending.

Project description:ObjectiveTo determine whether a polymorphism the in delta-aminolevulinic acid dehydratase (ALAD) gene modifies the neurotoxicity of lead in older adults.MethodsThe authors studied men participating in the Department of Veterans Affairs' Normative Aging Study, assessing their recent exposure to lead by measuring blood lead (n = 915) at each triennial clinic visit, and, beginning in 1991, assessing their cumulative exposure by measuring lead levels in tibia (n = 722) and patella (n = 720), using K-shell x ray fluorescence. Starting in 1993 and again at each triennial visit, the authors administered the Mini-Mental State Examination (MMSE) to assess their cognitive functioning. The relation of the lead biomarkers to MMSE score was evaluated and this association was compared among men who carried the variant allele, ALAD-2, versus men without the allele.ResultsSixteen per cent of men carried the ALAD-2 allele. Median tibia and patella lead levels (first-third quartile) were 19 (13-28) and 27 (18-39) microg/g. Blood lead levels were consistent with non-occupational exposure: only 6% of men had levels > or =10 microg/dl. In multivariable adjusted analyses, higher levels of blood lead were associated with poorer performance on the MMSE. This association was most pronounced among ALAD-2 carriers, among whom a 3 microg/dl increment in blood lead (the interquartile range) was associated with a 0.26 point lower mean MMSE score (95% CI -0.54 to 0.01), compared with a 0.04 point lower score (95% CI -0.16 to 0.07) among non-carriers. The modest 0.22 point difference in these associations did not attain statistical significance, however (p(interaction) = 0.13). The associations between bone lead levels and MMSE score did not vary by ALAD-2 status.ConclusionsAlthough not statistically significant, these findings suggest that ALAD genotype may modify blood lead's adverse association with cognition among older men who had community exposures to lead. However, despite a relatively large sample size and the use of sensitive methods for measuring lead burden, the evidence overall was fairly weak.

Dataset Information

Association between ?-aminolevulinate dehydratase G177C polymorphism and blood lead levels in brain tumor patients.

Publications

Association between δ-aminolevulinate dehydratase G177C polymorphism and blood lead levels in brain tumor patients.

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