Association of the alpha4 integrin subunit gene (ITGA4) with autism.
In the present work, we provide further evidence for the involvement of the integrin alpha-4 precursor gene (ITGA4) in the etiology of autism, by replicating previous findings of a genetic association with autism in various independent populations. The ITGA4 gene maps to the autism linkage region on 2q31-33 and is therefore a plausible positional candidate. We tested eight single nucleotide polymorphisms (SNPs) in the ITGA4 gene region for association with autism in a sample of 164 nuclear families. Evidence for association was found for the rs155100 marker (P = 0.019) and for a number of specific marker haplotypes containing this SNP (0.00053 < P < 0.022). alpha4 integrins are known to play a key role in neuroinflammatory processes, which are hypothesized to contribute to autism. In this study, an association was found between the ITGA4 rs1449263 marker and levels of a serum autoantibody directed to brain tissue, which was previously shown to be significantly more frequent in autistic patients than in age-matched controls in our population. This result suggests that the ITGA4 gene could be involved in a neuroimmune process thought to occur in autistic patients and, together with previous findings, offers a new perspective on the role of integrins in the etiology of autism to which little attention has been paid so far.
Correia
Catarina
C
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Coutinho
Ana M
AM
Almeida
Joana
J
Lontro
Raquel
R
Lobo
Cristina
C
Miguel
Teresa S
TS
Martins
Madalena
M
Gallagher
Louise
L
Conroy
Judith
J
Gill
Michael
M
Oliveira
Guiomar
G
Vicente
Astrid M
AM
D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001921:Brain / Q000276:immunology; D002889:Chromosomes, Human, Pair 2; D005192:Family Health; D056726:Genetic Association Studies; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D039441:Integrin alpha4 / Q000235:genetics*; D020078:Neurogenic Inflammation; D015213:Neuroimmunomodulation; D020641:Polymorphism, Single Nucleotide
D001323:Autoantibodies; D005819:Genetic Markers; D039441:Integrin alpha4