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Delta‐Aminolevulinic Acid Dehydratase (ALAD) polymorphism that modulates lead toxicity is increased among autistic children
Author(s) -
Palmer Shan,
Jernigan Stefanie,
Cleves Mario,
Melnyk Stepan,
James S. Jill
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1066-c
Subject(s) - genotype , glutathione , oxidative stress , toxicity , lead poisoning , dehydratase , odds ratio , medicine , chemistry , endocrinology , gene , biochemistry , enzyme , psychiatry
Chronic low dose exposure to lead in the environment has been associated with impaired cognitive development in children and adolescents. The risk of toxicity with low level lead exposure is likely to be determined, in part, by individual genetic susceptibility. The ALAD G177C polymorphism yields two co‐dominant alleles, ALAD‐1 and ALAD‐2, which have been implicated in susceptibility to lead toxicity. The ALAD 1‐2/2‐2 variants have been associated with higher lead levels in blood and tissues and may lead to oxidative damage. The frequency of ALAD1 and ALAD2 genotypes was evaluated in 400 autistic children and 247 controls using ABI PRISM 7700 sequence detection system and allele‐specific primer‐probe sets from ABI Assays by Design. Plasma levels of glutathione and the GSH/GSSG ratio were quantified using HPLC with electrochemical detection. The frequency of ALAD 1‐2/2‐2 was 20.9% among cases and 13.8% among controls with an odds ratio of 1.66 (95% CI: 1.06, 2.62; p<0.02). In addition, significant gene‐gene interactions were observed between ALAD 1‐2/2‐2 and the reduced folate carrier ( RFC1 A80G ), transcobalamin II ( TCN2 C776G ) and paroxonase 1 ( PON1 T172A) genotypes. Glutathione levels and the GSH/GSSG ratio were lower among the ALAD 1‐2/2‐2 autistic children. These results suggest that the frequency of ALAD 1‐2/2‐2 genotype is increased among autistic children and may further exacerbate oxidative stress.