title: Influence of the 5-HTTLPR polymorphism and environmental risk factors in a Brazilian sample of patients with autism spectrum disorders.
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.
authors.affiliation: Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Dânae
authors.initials: D
authors.lastname: Longo
authors.forename: Lavínia
authors.initials: L
authors.lastname: Schüler-Faccini
authors.forename: Ana Paula Carneiro
authors.initials: AP
authors.lastname: Brandalize
authors.forename: Rudimar
authors.initials: R
authors.lastname: dos Santos Riesgo
authors.forename: Claiton Henrique Dotto
authors.initials: CH
authors.lastname: Bau
mesh_terms: D000339:Affect / Q000502:physiology; D000704:Analysis of Variance; D001321:Autistic Disorder / Q000453:epidemiology* / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D004777:Environment; D004827:Epilepsy / Q000139:chemically induced; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D011795:Surveys and Questionnaires
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins