RESUMO
Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P=0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P=0.008 for total substitutions and P=0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.
Assuntos
Alelos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Receptores de Dopamina D4/genética , Adulto , Sequência de Aminoácidos/genética , Sequência de Bases , Criança , Éxons/genética , Feminino , Genótipo , Humanos , Masculino , Repetições Minissatélites/genética , Dados de Sequência MolecularRESUMO
The present study investigates possible associations between the 5-HTT control region polymorphism (5-HTTLPR) with adult ADHD, including subtypes, severity, temperament profile and comorbidities. The polymorphic site was genotyped in 312 adult patients with ADHD and 236 controls, all of them Brazilians of European descent. The interviews followed the DSM-IV criteria, using the K-SADS-E for ADHD and oppositional defiant disorder, SCID-I and MINI for comorbidities and the TCI for temperament dimensions. The 5-HTTLPR polymorphism was not associated with ADHD. Carriers of the S allele presented slightly higher inattention and novelty seeking scores, and a higher frequency of drug dependence. These differences do not persist after correction for multiple comparisons. These results suggest that the 5-HTTLPR polymorphism does not have a direct role in the predisposition to adult ADHD. There is suggestive evidence for a small effect in some behavioral phenotypes related to ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Fenótipo , Reação em Cadeia da PolimeraseRESUMO
The aim of the present study is to test for possible associations between the C-1291G polymorphism in the alpha2A-adrenergic receptor gene (ADRA2A) with tobacco smoking and alcohol dependence. The genotype and allele frequencies were compared in three groups of European-derived Brazilian males: individuals with co-occurrence of tobacco smoking and alcohol dependence (N = 110), with tobacco smoking (N = 121) and controls (N = 114). The frequency of the G allele was higher in the group with both conditions, intermediate among subjects with smoking, and lower among controls (chi(2) = 8.00; p = 0.02). The chi(2) partitioning did not reveal significant differences between the sample with the two conditions and the sample of smokers (chi(2) = 0.82; p = 0.36). Combining both groups, the difference to the non-smoking controls is higher than the one observed in the three-groups analysis (chi(2) = 7.18; p = 0.007). The results suggest a role for the ADRA2A C-1291G polymorphism, notably the G allele, in the predisposition to tobacco smoking. The influence of the ADRA2A gene in nicotine and other substance dependencies should be more extensively assessed in future studies.
Assuntos
Polimorfismo Genético/genética , Receptores Adrenérgicos alfa 2/genética , Fumar/genética , Adulto , Alcoolismo/complicações , Alcoolismo/genética , Alelos , DNA/genética , Feminino , Frequência do Gene , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
The T allele of the C825T polymorphism in the G-protein beta(3) subunit gene (GNB3) is related to the increase of signal transduction by the G-protein. G-proteins are intermediary paths in signal transduction from receptors involved in mood regulation and substance dependence. We studied the C825T polymorphism in individuals with (i) alcohol and nicotine dependence (n = 109), (ii) nicotine dependence only (n = 117) and (iii) non-dependent controls (n = 108). We also tested for possible associations with psychiatric comorbidities among alcohol-dependent individuals. No differences were detected for allele and genotype frequencies in individuals with or without dependencies. Alcohol-dependent individuals with the heterozygous genotype presented more frequently major depressive disorder (chi(2) = 12.34; p = 0.002). These findings, taken together with other studies suggesting an influence of the C825T polymorphism in major depressive disorder, support the hypothesis of the involvement of G-proteins in mood regulation.