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Re: genetic variations

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Hi, Sue.

Here's an abstract of her talk in San Diego last April:

" Experimental Biology 2005. April 2. San Diego . Abstract

Low plasma methionine, cysteine, and glutathione levels are

associated with increased frequency of common polymorphisms

affecting methylation and glutathione pathways in children with

autism

S. Jill , Stepan Melnyk, Stefanie Jernigan. Pediatrics,

University of Arkansas for Medical Sciences, 1120 Marshall St. ,

Slot 512.40B, Little Rock , AR , 72202

Autism is a complex neurodevelopmental disorder that is thought to

involve both genetic and environmental factors. The 10-fold increase

in the prevalence of autism in the last 15 years is a major public

health concern. Although abnormal thiol metabolism has been

associated with other neurologic diseases, these pathways and

related polymorphisms have not been evaluated in autistic children.

Plasma levels of metabolites in methionine transmethylation and

transsulfuration pathways were measured in 90 autistic and 45

control children using HPLC with electrochemical detection.

Polymorphic variants in transcobalamin II (TCII), methylene-

tetrahydrofolate reductase (MTHFR), methionine synthase reductase

(MTRR), catecholamine-O-methyltransferase (COMT), and glutathione-S-

transferase (GST) M1/T1 were evaluated in 233 autistic children and

183 controls.

The results indicated that mean levels of methionine, cysteine,

total glutathione, and the ratio of oxidized to reduced glutathione

were significantly decreased among the autistic children.

The frequency of MTHFR 677CT/1298AG heterozygosity, TCII 776GG, COMT

1947GG, and the GST M1/T1 double null genotype was increased in the

autistic children relative to controls.

We hypothesize that an increased vulnerability to oxidative stress

(environmental and/or intracellular) may contribute to the

development and clinical manifestations of autism.

Supported by the Autism Research Institute, San Diego , CA "

Rich

> Hi Rich,

>

> You wrote, " My current suspicion is that most people who go low

in

> glutathione start out with inherited genetic variations that make

it

> difficult for their bodies to maintain the normal glutathione

level.

> (This has been shown in autism by Jill and coworkers... "

>

> I found more about Jill here:

>

> http://www.forbes.com/lifestyle/health/feeds/hscout/2005/04/03/

> hscout524907.html

>

> " and her team also looked at changes that occur in several

genes

> that could affect glutathione metabolism in blood samples from

233

> autistic children, vs. 183 children without autism. They found

changes

> in three genes more often in the children with autism. said

these

> are common genes that don't cause autism, but they could

contribute to

> the development of these metabolic abnormalities. "

>

> Rich, do you know which three genes these are?

>

> Sue ,

> Upstate New York

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