Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes
| Autor: | Tiziana Pascucci, Riccardo Alessandrelli, Valerio Napolioni, Stefano Puglisi-Allegra, Roberto Sacco, Patricia Lewin, Paolo Curatolo, C. Lenti, Carmela Bravaccio, Karl L. Reichelt, Raun Melmed, Barbara Manzi, Cindy Schneider, Roberto Militerni, Federica Lombardi, Antonio M. Persico, Monica Saccani, Francis Rousseau |
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| Přispěvatelé: | Napolioni, V, Lombardi, F, Sacco, R, Curatolo, P, Manzi, B, Alessandrelli, R, Militerni, R, Bravaccio, Carmela, Lenti, C, Saccani, M, Schneider, C, Melmed, R, Pascucci, T, Puglisi Allegra, S, Reichelt, Kl, Rousseau, F, Lewin, P, Persico, A. M. |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Serotonin Candidate gene Adolescent Endophenotypes Quantitative Trait Loci autism integrin-beta 3 quantitative trait locus SLC6A4 serotonin serotonin transporter Autistic Disorder Child Preschool Female Haplotypes Humans Infant Integrin beta3 Introns Linkage Disequilibrium Polymorphism Single Nucleotide Regression Analysis Serotonin Plasma Membrane Transport Proteins Young Adult Genetic Predisposition to Disease Locus (genetics) Quantitative trait locus Biology Polymorphism Single Nucleotide Article integrin-βb 3 slc6a4 Genetics medicine Pervasive developmental disorder Genetics (clinical) Child Preschool Haplotype medicine.disease Settore MED/39 - Neuropsichiatria Infantile Developmental disorder Autism spectrum disorder Autism |
| Zdroj: | European Journal of Human Genetics. 19:353-359 |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/ejhg.2010.180 |
| Popis: | 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 P=0.038). Haplotype H3 is largely over-transmitted to the affected offspring and doubles the risk of an ASD diagnosis (HBAT P=0.005; odds ratio (OR)=2.000), at the expense of haplotype H1, which is under-transmitted (HBAT P=0.018; OR=0.725). 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 (P=0.008). 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, P=0.001; multiple regression analysis, P=0.010). 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. |
| Databáze: | OpenAIRE |
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