Article

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: 2.83). 04/2009; 1267:9-17. DOI: 10.1016/j.brainres.2009.02.072
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
104 Views
  • [Show abstract] [Hide abstract]
    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.
    Gene 09/2014; 553(1). DOI:10.1016/j.gene.2014.09.058 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Perinatal and background risk factors for autism were identified in a cohort of autistic children in Zhengzhou, China, to formulate preventative and treatment strategies for high-risk families. In this case-control study, children were screened for suspected autism using the Autism Behavior Checklist (ABC) and diagnosed according to DSM-IV and the Childhood Autism Rating Scale (CARS). We collected perinatal histories and clinical data of 286 confirmed autistic children treated at the Third Affiliated Hospital Children׳s Psychological Clinic of Zhengzhou University from 2011 to 2013. The control group consisted of 286 healthy children from area kindergartens. Maternal age>30 years, parental introversion as measured by the Eysenck Personality Questionnaire, low level of parental education, smoking, abortion threat, pregnancy complications, maternal illness during pregnancy, maternal mental health, family history of mental illness, neonatal jaundice, birth asphyxia, premature rupture of the fetal membrane, and gestational age<37 weeks were significantly higher in the autism group. These factors were significantly correlated with behavioral symptoms as measured by ABC scores (Kendall rank correlation). Birth asphyxia, neonatal jaundice, maternal age, parental introversion, family history of mental illness, abortion threat, premature delivery, and smoking were identified as independent risk factors by multivariate logistic regression.
    Psychiatry Research 06/2014; DOI:10.1016/j.psychres.2014.05.057 · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Presence of platelet hyperserotonemia and effective amelioration of behavioral dysfunctions by selective serotonin reuptake inhibitors (SSRI) in autism spectrum disorders (ASD) indicate that irregularities in serotonin (5-HT) reuptake and its homeostasis could be the basis of behavioral impairments in ASD patients. SLC6A4, the gene encoding serotonin transporter (SERT) is considered as a potential susceptibility gene for ASD, since it is a quantitative trait locus for blood 5-HT levels. Three functional polymorphisms, 5-HTTLPR, STin2 and 3'UTR-SNP of SLC6A4 are extensively studied for possible association with the disorder, with inconclusive outcome. In the present study, we investigated association of these polymorphisms with platelet 5-HT content and symptoms severity as revealed by childhood autism rating scale in ASD children from an Indian population. Higher 5-HT level observed in ASD was highly significant in children with heterozygous and homozygous genotypes comprising of minor alleles of the markers. Quantitative transmission disequilibrium test demonstrated significant genetic effect of STin2 allele as well as STin2/3'UTR-SNP and 5-HTTLPR/3'UTR-SNP haplotypes on 5-HT levels, but no direct association with overall CARS score and ASD phenotype. Significant genetic effect of the markers on specific behavioral phenotypes was observed for various sub-phenotypes of CARS in quantitative trait analysis. Even though the 5-HT level was not associated with severity of behavioral CARS score, a significant negative relationship was observed for 5-HT levels and level and consistency of intellectual response and general impression in ASD children. Population-based study revealed higher distribution of the haplotype 10/G of STin2/3'-UTR in male controls, suggesting protective effect of this haplotype in male cases. Overall results of the study suggest that SLC6A4 markers have specific genetic effect on individual ASD behavioral attributes, might be through the modulation of 5-HT content.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2014; DOI:10.1016/j.pnpbp.2014.09.004 · 4.03 Impact Factor