NEW YORK (Reuters Health) - Single nucleotide polymorphisms (SNPs) within the mitochondrial aspartate/glutamate carrier SLC25A12 gene are strongly associated with autism, according to a report in the April issue of the American Journal of Psychiatry.
“Autism appears to be largely genetic,” Dr. Joseph D. Buxbaum from the Mount Sinai School of Medicine, New York, told Reuters Health. “Genetic testing should ultimately be available to identify people at high risk.”
Based on their recent mapping of a susceptibility locus for autism to chromosome region 2q24-q33, Dr. Buxbaum and colleagues analyzed genes across this interval to identify an autism susceptibility gene in 411 families.
Among nine genes analyzed in this region, the authors report, only two SNPs, both within the SLC25A12 gene, differed significantly between autistic and nonautistic subjects using both allele-based and genotype-based tests.
Among 411 families studied, 197 had at least one parent heterozygous for at least one of these SNPs, the report indicates.
Whether looking at these SNPs in one affected individual per family or in all affected individuals, the researchers note, there was an increased transmission of the G*G haplotype in autism.
“The evidence for both linkage and association support a role for SLC25A12 as an autism susceptibility gene (rather than a modifying gene,” the authors conclude.
The protein encoded by SLC25A12 “is critically involved in the activity of the malate/aspartate NADH shuttle, catalyzing the electrogenic exchange of aspartate for glutamate and a proton, and is also involved in the urea cycle,” the investigators explain. “Dysfunction of this protein, or altered expression of this protein, may lead to an alteration in mitochondrial function and ATP synthesis.”
These findings carry significant clinical implications. “If we can find the first few genes that contribute several-fold risk, it may be possible, by analyzing all these genes together, to define people with a many-fold increase in risk,” Dr. Buxbaum said.
“Those people could then be treated at the earliest possible age using behavioral methods that can be beneficial. In addition, if confirmed, the current finding supports a role for mitochondrial function in autism, and this may be a therapeutic avenue,” he added.
Source: Am J Psychiatry 2004;161:1-8. [ Google search on this article ]
MeSH Headings:Polymorphism, Single NucleotideCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
