Objectives: We aimed at assessing the association between ITGB3 gene variants and autism spectrum disorders. In addition, we also analyzed the influence of ITGB3 gene variants on serotonin plasma levels.
Methods: Our sample includes 281 simplex and 12 multiplex families, encompassing 306 patients with an autism spectrum disorder. Nine SNPs spanning the ITGB3 locus were genotyped using SNPlex and TaqMan technologies. Family-based association analyses were performed using FBAT and UNPHASED.
Results: One ITGB3 haplotype is significantly associated with autism (HBAT, global P<0.05) and doubles the risk of affection (O.R.=2.11, P<0.01). The “risk” and “protective” haplotypes differ only by a single SNP, rs12603582, which analyzed by itself reaches P-values of 0.071 and 0.056 with FBAT and TDT, respectively. Effects of ITGB3 alleles and ITGB3-SLC6A4 interactions on serotonin blood levels do not reach statistical significance (P=0.12).
Conclusions: Family-based association analysis shows that in our sample one ITGB3 gene variant determines an approximately 2-fold increase in risk of developing autism. These results provide further evidence of ITGB3 involvement in autism spectrum disorders. Further analyses are underway to assess ITGB3-SLC6A4 interactions in reference to affection status.