Association between methylation status of CpG island in DAT1 and DRD4 genes and clinical symptoms of ADHD / 中国神经精神疾病杂志

Objective To investigate the correlation of methylation status in DA T1 and DRD4 genes and severity of clinical manifestations in ADHD patients.Methods One hundrd eleven DSM-Ⅳ defined ADHD patients were enrolled in this study and the demographic data were collected.Clinical symptoms were also assessed by Attention Deficit Hyperactivity Disorder Rating Scale-Ⅳ Home Version (ADHD-RS-Ⅳ) and self-developed Oppositional Defiant Disorder (ODD) rating scale.Bisulfite genomic sequencing (BGS) was used to detect the methylation status of every CpG site in DA T1 and DRD4 promoter CpG island in peripheral venous blood.Results The DNA methylation level in total CpG island for DA T1 was higher in individuals without depression,anxiety or ADHD family history compared to individuals with above family histories (P＜0.05).The differences on methylation levels for DA T1 and DRD4 were not significant between high and low ADHD-RS-Ⅳ total score (≤30 vs.＞30),ADHD-RS-Ⅳ inattention score (≤ 17 vs.＞17),and ADHD-RS-Ⅳ hyperactivity/impulsivity score (≤13 vs.＞13) subgroups (all P＜0.05).The methylation levels in total CpG island in DA T1 was higher in individuals whose ODD score were ＜9 compared to those whose ODD score were ≥9 (P＜0.05).Conclusions Methylation status of CpG island in DAT1 may influence the severity of oppositional defiant symptom in ADHD patients,which is correlated with depression,anxiety and ADHD family histories.

Molecular genetic case-control women investigation from the first Brazilian high-risk study on functional psychosis / Investigação genético-molecular do tipo caso-controle em uma amostra de mulheres portadoras de psicose funcional do primeiro estudo de alto-risco brasileiro

OBJECTIVE: Data from epidemiological studies have demonstrated that genetics is an important risk factor for psychosis. The present study is part of a larger project, pioneer in Brazil, which has been conducted by other researchers who intend to follow a high-risk population (children) for the development of schizophrenia and bipolar disorder. In this first phase of the project, the objective was to investigate the distribution of four candidate genetic polymorphisms for functional psychosis (Ser9Gly DRD3, 5HTTLPR, the VNTR 3'-UTR SLC6A3 and Val66Met BDNF) in a case-control sample. METHOD: A total of 105 women (58 with schizophrenia and 47 with bipolar disorder) and 62 gender-matched controls were investigated. RESULTS: Allele and genotype distributions of all identified functional polymorphisms did not differ statistically between cases and controls. CONCLUSIONS: These results suggest that the investigated polymorphisms were not related to susceptibility to functional psychoses in our Brazilian sample. These findings need to be validated in larger and independent studies.

OBJETIVO: Estudos epidemiológicos demonstram que alterações genéticas são fatores de risco importantes para o desenvolvimento de psicose. O presente estudo é parte um projeto maior, pioneiro no Brasil, realizado com mais pesquisadores, que pretende seguir uma população de alto risco genético para o desenvolvimento de esquizofrenia e transtorno bipolar. Nesta primeira fase, o objetivo foi investigar a distribuição de quatro polimorfismos genéticos candidatos no desenvolvimento de psicose funcional (Ser9Gly DRD3, 5HTTLPR, o VNTR 3'-UTR SLC6A3 e Val66Met BDNF) em uma amostra caso-controle. MÉTODO: O estudo genético respeitou o desenho metodológico do estudo clínico. Um total de 105 mulheres (58 esquizofrenia e 47 transtorno bipolar) e 62 controles sem diagnóstico psiquiátrico foi investigado. RESULTADOS: Nenhuma diferença estatisticamente significante foi observada nas distribuições alélicas e genotípicas entre os grupos investigados. CONCLUSÕES: Os resultados sugerem que estes polimorfismos não estavam relacionados à suscetibilidade para psicose funcional nesta amostra brasileira estudada. Esses achados precisam ser validados em estudos maiores e independentes.

Polymorphism of Dopamine Transporter Gene(DAT1) in Korean Social Phobia Patients: Preliminary Study

OBJECTIVE: Although polymorphism of dopamine transporter gene(DAT1) has been considered to be implicated in the pathogenesis of social phobia, previous investigations have been inconsistent and controversial. The authors investigated the relationship between DAT1 polymorphism and social phobia in Koreans. METHODS: DAT1 and alleles of fifty subjects who met DSM-IV criterion of social phobia, and those of age- & sex- matched fifty normal controls in Korea were compared. Additionally, patients were grouped into generalized(33) and nongeneralized(17) types and DAT1 polymorphism was compared with that of age- & sex- matched controls. DAT1 with variable number of tandem repeats(VNTR) were determined by using polymerase chain reaction. To compare the distribution of the DAT1 polymorphism between different groups, Fisher`s exact test was used. RESULTS: There were no significant differences in either genotypic(p=0.451) or allelic(p=0.452) distributions between the social phobia patients and the controls. There also were no differences in genotypic distribution between subtypes of social phobia patients and the controls. CONCLUSION: We couldn't find any association between DAT1 polymorphism and social phobia. Further studies including larger number of samples and diverse clinical variables should be conducted to elucidate the present findings.