Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes

Valerio Napolioni, Federica Lombardi, Roberto Sacco, Paolo Curatolo, Barbara Manzi, Riccardo Alessandrelli, Roberto Militerni, Carmela Bravaccio, Carlo Lenti, Monica Saccani, Cindy Schneider, Raun Melmed, Tiziana Pascucci, Stefano Puglisi-Allegra, Karl Ludvig Reichelt, Francis Rousseau, Patricia Lewin, Antonio M. Persico

Research output: Contribution to journalArticlepeer-review


The integrin-Β 3 gene (ITGB3), located on human chromosome 17q21.3, was previously identified as a quantitative trait locus (QTL) for 5-HT blood levels and has been implicated as a candidate gene for autism spectrum disorder (ASD). We performed a family-based association study in 281 simplex and 12 multiplex Caucasian families. ITGB3 haplotypes are significantly associated with autism (HBAT, global P0.038). Haplotype H3 is largely over-transmitted to the affected offspring and doubles the risk of an ASD diagnosis (HBAT P0.005; odds ratio (OR)2.000), at the expense of haplotype H1, which is under-transmitted (HBAT P0.018; OR0.725). These two common haplotypes differ only at rs12603582 located in intron 11, which reaches a P-value of 0.072 in single-marker FBAT analyses. Interestingly, rs12603582 is strongly associated with pre-term delivery in our ASD patients (P0.008). On the other hand, it is SNP rs2317385, located at the 5′ end of the gene, that significantly affects 5-HT blood levels (Mann-Whitney U-test, P0.001; multiple regression analysis, P0.010). No gene-gene interaction between ITGB3 and SLC6A4 has been detected. In conclusion, we identify a significant association between a common ITGB3 haplotype and ASD. Distinct markers, located toward the 5′ and 3′ ends of the gene, seemingly modulate 5-HT blood levels and autism liability, respectively. Our results also raise interest into ITGB3 influences on feto-maternal immune interactions in autism.

Original languageEnglish
Pages (from-to)353-359
Number of pages7
JournalEuropean Journal of Human Genetics
Issue number3
Publication statusPublished - Mar 2011


  • autism
  • integrin-βb 3
  • quantitative trait locus
  • serotonin
  • serotonin transporter
  • SLC6A4

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


Dive into the research topics of 'Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes'. Together they form a unique fingerprint.

Cite this