Association between δ-aminolevulinate dehydratase G177C … · 2016-06-17 · Association between...
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Association between δ-aminolevulinate dehydratase G177C polymorphism and blood lead levels in brain tumor patients MAHMOUD M. TAHA 1 , OSAMA ABD EL AZIZ GABER 2 , NORHAN ABDALLA SABBAH 2 Departments of Neurosurgery (1) and Medical Biochemistry (2) , Faculty of Medicine, Zagazig University, Zagazig, Egypt
Transcript of Association between δ-aminolevulinate dehydratase G177C … · 2016-06-17 · Association between...
Association between δ-aminolevulinate dehydratase G177C polymorphism and blood lead levels in brain
tumor patients
MAHMOUD M. TAHA1, OSAMA ABD EL AZIZ GABER2,
NORHAN ABDALLA SABBAH2
Departments of Neurosurgery(1) and Medical Biochemistry(2), Faculty of Medicine, Zagazig University, Zagazig, Egypt
Background
Lead heavy metals 15-20mg/kg earth s crust
2% blood
99% erythrocytes 1% plasma
94% bone
Biological half life
Blood 30 days bone 10 -27 years
US and Europe 30-50ug/m3 of air
CNS and PNS
Acue toxicity chronic toxicity
Background
Community and occupational exposures of adults to
lead has been recognized for centuries, particularly in
Egypt, as unfavorable effects on the hematopoietic,
gastrointestinal, urinary, cardiovascular and nervous
systems have been well-documented.
(Agency for Toxic Substances and Disease Registry (ATSDR): Toxicological profile for lead. U.S.
Department of Health and Human Services, Atlanta, GA, USA 1999)
The International Agency Research onCancer inorganic lead a ‘probable’
human carcinogen.IARC WG: Vol. 87. World Health Organization, Lyon, France, 2006.
Certain epidemiological studies havereported an increased risk of braintumors with potential lead exposure,particularly meningioma, another studyhas reported no significant associationbetween lead and brain cancer.
Background
Genetic factors elucidate the differences in symptoms betweenindividuals who have had similar lead exposures. Identification ofsuch genes would aid in the explanation of variation in theassociation between biological markers of lead exposure andmeasures of organ dysfunction.
The δ-aminolevulinic acid dehydratase (ALAD) gene codes for theenzyme ALAD the second step of heme synthesis.
Polymorphism in the gene ALAD G177C G-to-C transversion atposition 177 of the coding region, resulting in the substitution ofasparagine for lysine.
ALAD1
ALAD G177C
ALAD2 .
ALAD
lead, trichloroethylene, bromobenzene, styrene
ALAD2 allele have been shown to exhibit higher blood
lead levels compared with the ALAD1 homozygotes,
possibly due to tighter binding of lead by the ALAD2
enzyme.Shen XM, et al: Environ Res 85: 185-190, 2001.
Background
Background
ALAD genotype distribution of lead to target organs remains unknown.
It has been documented that the binding of lead molecules inactivates δ-ALAD and
causes a rise in the levels of its substrate, δ-ALA .
In the brain, excess δ-ALA disrupts the γ-aminobutyric acid/glutamate system in
several ways, creating potential for neuroexcitotoxic events and cell death
Villayandre BM,. Brain Res 1061: 80-87, 2005.
Materials and Methods
81 patients with brain tumors
Primary – adult
41 gliomas,31 meningeoma,9 others
81 gender and age matched healthy control subjects.
Participants.
All the participants
History; demographic
Examination;
Complete neurological examination.
Radiological investigations by computed tomography and magnetic resonance imaging
post operative histopathology
Materials and Methods
Atomic absorption spectroscopic measurement of
blood lead
DNA extraction. DNA was isolated and purified
from whole blood (EDTA) using the
manufacturer's instructions (Qiagen
GmbH, Hilden, Germany).
Genotyping of ALAD G177C gene
polymorphism. A polymerase
PCR
Results
Results
Results
Results
Results
The homogenous racial cohort limited the confounding genetic factorscaused by ethnic heterogeneity.
The results of the present study supported the suggestion that ALADG177C gene polymorphism contributed to increase the susceptibility andthe development of brain tumors. This conclusion is based on theobservation that ALAD2 carriers are higher in brain tumor patientsespecially meningioma.
Identifying a biomarker of increased risk could provide a tool forprimary prevention, and may suggest mechanisms to target forintervention.
More care and attention have to be applied to the lead exposure in theEgyptian community as the results of the present study indicated that theEgyptians are at grossly increased risk of lead exposure.
Conclusions and Recommendations
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