The Frequency of Polymorphisms affecting Lead and Mercury Toxicity among Children with Autism

Author: Rose S, Melnyk S, Savenka A, Hubanks A, Jernigan S, Cleves M, James SJ.

Source: American Journal of Biochemistry & Biotechnology.

Year: 2008

Comment:

The researchers note, "In summary, we have demonstrated that some autistic children have a significant increase in the frequency of the ALAD 2 variant allele that may underlie differential susceptibility to lead toxicity in these children. These data support the possibility that a genetic predisposition may increase vulnerability to lead toxicity during critical windows of prenatal and post-natal neurodevelopment."

Abstract / Excerpt:

“Individual risk of developmental neurotoxicity with exposure to environmentally relevant levels of lead and mercury is likely to be determined by genetic susceptibility factors as well as additive interactions with other environmental pollutants, cumulative dose, and the developmental stage of exposure. The apparent increase in autism diagnosis over the last 15 years has enhanced interest in the possibility that an environmental trigger may be required to uncover the genetic liability in some cases of autism. The exquisite sensitivity of the developing brain and immune system to very low levels of lead and mercury give this hypothesis biologic plausibility. Delta aminolevulinic acid dehydratase (ALAD) and coproporphyin oxidase (CPOX) are two enzymes inhibited by low levels of lead and mercury, respectively. Common polymorphisms in these genes have been associated with elevated blood levels of lead and mercury and could potentially increase vulnerability to prenatal and/or postnatal developmental neurotoxicity. To explore this possibility, the frequency of the ALAD2 variant and variants in CPOX-4 and CPOX-5 were evaluated in 450 autistic children and 251 unaffected controls. A significant increase in the frequency of the ALAD2 allele was observed; however, contrary to our hypothesis, the frequency of both CPOX variants was significantly lower among the autistic children. Both lead and mercury induce oxidative stress by depleting the major intracellular antioxidant, glutathione. Among 242 autistic children with the variant ALAD2 allele, significant decreases in plasma glutathione and in the glutathione redox ratio were observed. These results suggest that children with autism who inherit the ALAD2 allele with lower glutathione levels may be at increased risk for lead toxicity during prenatal and postnatal neurodevelopment.”

Citation:

Rose S, Melnyk S, Savenka A, Hubanks A, Jernigan S, Cleves M, James SJ. The frequency of polymorphisms affecting lead and mercury toxicity among children with autism. American Journal of Biochemistry & Biotechnology. 2008; 4(2).