Background
Autism is a severe developmental disorder, with strong genetic underpinnings. Previous
genome-wide scans unveiled a linkage region spanning 3.5 Mb, located on human chromosome
3p25. This region encompasses the ATP2B2 gene, encoding the plasma membrane calcium-transporting ATPase 2 (PMCA2), which extrudes
calcium (Ca2+) from the cytosol into the extracellular space. Multiple lines of evidence support
excessive intracellular Ca2+ signaling in autism spectrum disorder (ASD), making ATP2B2 an attractive candidate gene.
Methods
We performed a family-based association study in an exploratory sample of 277 autism
genetic resource exchange families and in a replication sample including 406 families
primarily recruited in Italy.
Results
Several markers were significantly associated with ASD in the exploratory sample,
and the same risk alleles at single nucleotide polymorphisms rs3774180, rs2278556,
and rs241509 were found associated with ASD in the replication sample after correction
for multiple testing. In both samples, the association was present in male subjects
only. Markers associated with autism are all comprised within a single block of strong
linkage disequilibrium spanning several exons, and the “risk” allele seems to follow
a recessive mode of transmission.
Conclusions
These results provide converging evidence for an association between ATP2B2 gene variants and autism in male subjects, spurring interest into the identification
of functional variants, most likely involved in the homeostasis of Ca2+ signaling. Additional support comes from a recent genome-wide association study by
the Autism Genome Project, which highlights the same linkage disequilibrium region
of the gene.
Key Words
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Article info
Publication history
Published online: July 15, 2011
Accepted:
May 8,
2011
Received in revised form:
March 16,
2011
Received:
December 15,
2010
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
