Converging evidence for an association of ATP2B2 allelic variants with autism in male subjects

Jérme Carayol, Roberto Sacco, Frédéric Tores, Francis Rousseau, Patricia Lewin, Jorg Hager, Antonio M. Persico

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 (Ca 2+) from the cytosol into the extracellular space. Multiple lines of evidence support excessive intracellular Ca 2+ 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 Ca 2+ 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.

Original languageEnglish
Pages (from-to)880-887
Number of pages8
JournalBiological Psychiatry
Volume70
Issue number9
DOIs
Publication statusPublished - Nov 1 2011

Fingerprint

Autistic Disorder
Linkage Disequilibrium
Genes
Plasma Membrane Calcium-Transporting ATPases
Alleles
Genome
Genome-Wide Association Study
Extracellular Space
Human Chromosomes
Cytosol
Italy
Single Nucleotide Polymorphism
Exons
Homeostasis
Calcium
Autism Spectrum Disorder

Keywords

  • ATP2B2
  • autistic disorder
  • calcium
  • gender heterogeneity
  • pervasive developmental disorders
  • PMCA2

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Carayol, J., Sacco, R., Tores, F., Rousseau, F., Lewin, P., Hager, J., & Persico, A. M. (2011). Converging evidence for an association of ATP2B2 allelic variants with autism in male subjects. Biological Psychiatry, 70(9), 880-887. https://doi.org/10.1016/j.biopsych.2011.05.020

Converging evidence for an association of ATP2B2 allelic variants with autism in male subjects. / Carayol, Jérme; Sacco, Roberto; Tores, Frédéric; Rousseau, Francis; Lewin, Patricia; Hager, Jorg; Persico, Antonio M.

In: Biological Psychiatry, Vol. 70, No. 9, 01.11.2011, p. 880-887.

Research output: Contribution to journalArticle

Carayol, J, Sacco, R, Tores, F, Rousseau, F, Lewin, P, Hager, J & Persico, AM 2011, 'Converging evidence for an association of ATP2B2 allelic variants with autism in male subjects', Biological Psychiatry, vol. 70, no. 9, pp. 880-887. https://doi.org/10.1016/j.biopsych.2011.05.020
Carayol, Jérme ; Sacco, Roberto ; Tores, Frédéric ; Rousseau, Francis ; Lewin, Patricia ; Hager, Jorg ; Persico, Antonio M. / Converging evidence for an association of ATP2B2 allelic variants with autism in male subjects. In: Biological Psychiatry. 2011 ; Vol. 70, No. 9. pp. 880-887.
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