Influence of the 5-HTTLPR polymorphism and environmental risk factors in a Brazilian sample of patients with autism spectrum disorders
Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Brazil.Brain research (Impact Factor: 2.84). 04/2009; 1267:9-17. DOI: 10.1016/j.brainres.2009.02.072
The 5-HTTLPR polymorphism of serotonin transporter gene is widely investigated in association studies in autism spectrum disorders (ASD). The results of such studies, however, remain controversial possibly due to the great genetic heterogeneity related to ASD and the lack of evaluation of the triallelic functional structure of 5-HTTLPR. This study tested for association between the 5-HTTLPR and ASD in a Brazilian sample by case-control and family-based association test (FBAT) methods, considering the biallelic and triallelic structures of this polymorphism. In addition, we performed an exploratory analysis of associations between specific clinical outcomes of ASD patients and 5-HTTLPR as well as several prenatal environmental factors. Genotyping was achieved in 151 ASD patients, 179 unrelated controls and 105 complete trios. There was no evidence of association between the 5-HTTLPR with ASD in both case-control and FBAT tests, but the LaLa 5-HTTLPR genotype was associated with mood instability in patients (P=0.006). The prenatal exposure to potential neuroteratogenic drugs was associated with epilepsy (P<0.001). Our findings suggest that the 5-HTTLPR is not associated with ASD in the Brazilian population, even considering the triallelic structure. Additionally, this study suggested a role of the 5-HTTLPR and environmental factors in the clinical expression of ASD.
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- "The research protocol and exclusion criteria also followed Longo et al. (2009). The presence of fragile X syndrome and other genetic syndromes , chromosomal abnormalities and lesional abnormalities of SNC was used as exclusion criteria. "
ABSTRACT: Autism Spectrum Disorders (ASDs) represent a group of very complex early-onset neurodevelopmental diseases. In this study, we analyzed 5 SNPs (rs2317385, rs5918, rs15908, rs12603582, rs3809865) at the β3 integrin locus (ITGB3), which has been suggested as a possible susceptibility gene, both as single markers and as part of haplotypes in 209 ASD children and their biological parents. We tested for association with the following: a) DSM-IV ASD diagnosis; b) clinical symptoms common in ASD patients (repetitive behaviors, echolalia, seizures and epilepsy, mood instability, aggression, psychomotor agitation, sleep disorders); and c) dimensional scores obtained with the Autism Screening Questionnaire and the Childhood Autism Rating Scale. These hypotheses were investigated using family-based tests, logistic regression models and analysis of covariance. The family-based tests showed an association with the H5 haplotype (composed by GTCGA alleles, the order of SNPs as above), which was transmitted less often than expected by chance (P=0.006; Pcorr=0.036). The analyses of the clinical symptoms showed a trend for an association with rs12603582 (P=0.008; Pcorr=0.064) and positive results for the haplotype composed of rs15908 and rs12603582 (Pglcorr=0.048; Pindcorr=0.015), both in symptoms of echolalia. Other nominal associations with different variants were found and involved epilepsy/seizures, aggression symptoms and higher ASQ scores. Although our positive results are not definitive, they suggest small effect associations of the ITGB3 gene with both ASD diagnosis and symptoms of echolalia. Other studies are nonetheless needed to fully understand the involvement of this locus on the etiology of ASDs and its different clinical aspects.
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ABSTRACT: OBJETIVOS: O presente estudo refere-se a uma revisão sistemática, cujo objetivo foi conduzir uma análise da produção científica de autores brasileiros sobre Transtornos do espectro autista (TEA), no período de 2002 a 2009. MÉTODOS: A busca bibliográfica foi realizada nas bases de dados: PUBMED, SciELO, LILACS e portal CAPES, incluindo diversos descritores, tais como autismo e transtorno invasivo do desenvolvimento. RESULTADOS: Um total de 93 artigos foi identificado, tendo sido publicados, sobretudo por autores da região Sudeste e de universidades públicas. Aproximadamente um terço dos artigos foi publicado em revistas com algum fator de impacto variando entre 0,441 e 3,211; sendo a maioria dos artigos baseada em amostras pequenas. Foram identificadas 140 dissertações e teses; 82,1% eram dissertações de mestrado. O principal tema de pesquisa abordado neste material relacionou-se a programas de intervenção para TEA. CONCLUSÃO: Esta revisão mostra o interesse de pesquisadores brasileiros na temática dos TEA, entretanto, uma parte considerável dessa produção científica se concentra em dissertações/teses e a minoria em artigos científicos publicados em revistas com elevado fator de impacto. Os resultados desta revisão sistemática mostram a necessidade de novos estudos com amostras maiores que levariam a um maior impacto e visibilidade da produção científica brasileira relativa aos TEA.
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ABSTRACT: This systematic review sought to conduct a general analysis of the Brazilian scientific output on autism spectrum disorders (ASD) published between 2002 and 2009. A literature search was conducted in the scientific databases PubMed, SciELO, and LILACS and in the CAPES portal, using keywords such as "autism" and "pervasive developmental disorders". A total of 93 articles were identified, most of which were authored by researchers from Southeast Brazil and affiliated with public universities. Approximately one-third of all articles were published in journals with an impact factor ranging from 0.441 to 3.211; most were based on small sample sizes. Furthermore, 140 theses and dissertations were identified, 82.1% of which were master's theses. Interventions for ASD were the predominant research topic. Brazilian researchers are clearly interested in the topic of ASD; however, a substantial portion of their scientific output is limited to doctoral dissertations or master's theses. A minority of articles was published in journals with a high impact factor. These findings suggest the need for studies with larger sample sizes, which could produce higher-impact findings and thus increase visibility of the Brazilian scientific output in the field of ASD research.
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