Receptor Gene Polymorphisms

Objective: Attention deficit hyperactivity disorder (ADHD) is a developmental disorder which is characterized by inattention, impulsiveness, and hyperactivity. The etiology of ADHD is not completely understood, but it is well known that the disorder has a moderate to high genetic component, with an estimated heritability of 76%. Polymorphic variants in several genes involved in regulation of the dopamine and related neurotransmitter pathways have been reported to be associated with ADHD. In this research we aimed to investigate the relationship between adult ADHD and DAT1 (dopamine transporter), DRD4 (dopamine D4 receptor), DRD3 (dopamine D3 receptor) gene polymorphisms.Method: Our study comprised unrelated 79 subjects who met DSM-IV criteria for adult ADHD and 75 controls and all were living in Denizli. All of the patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. With written informed consent, a blood sample was drawn from each subject individual. Venous blood samples were collected in ethylene diamine tetra acetic acid (EDTA) containing tubes. DNA was extracted from whole blood and genetic analyses were performed as described in the literature by using Polymerase Chain Reaction method. SSPSS 15.0 for Windows was used for statistical analyses.Results: Twenty-three of ADHD patients were defined as predominantly inattentive type, 22 of ADHD patients were defined as predominantly hyperactive-impulsive, and the rest of them were defined as combined type ADHD. 10/10 and 9/10 repeats were most relevant genotypes in both study and control group for DAT1 VNTR (variable number of tandem repeat) polymorphism. 4/4 and 4/7 repeats were mostly found in both study and control groups for DRD47- repeat allele gene polymorphism. Ser/Ser polymorphism was the most relevant genotype in both study and control group for DRD3 Ser9Gly gene polymorphism. DAT1 VNTR, DRD3 Ser9Gly, and DRD4 7- repeat allele gene polymorphisms were not associated with ADHD. These gene polymorphisms were also not associated with subtypes of ADHD.Conclusions: We couldn't detect any association between DAT1 VNTR, DRD3 Ser9Gly, and DRD4 7- repeat allele gene polymorphisms and adult ADHD. Ethnicity and sample size are important factors at case control type genetic studies. European studies mostly reported an association between polymorphism of these genes and ADHD, but majority of Middle Eastern and Asian studies didn't report such an association between these genes and ADHD. Multi centered future studies using genome wide scan and variable tandem repeat techniques with larger samples would be helpful for understanding the role of dopaminergic system at ADHD genetics

Receptor Gene Polymorphisms

Objective: Attention deficit hyperactivity disorder (ADHD) is a developmental disorder which is characterized by inattention, impulsiveness, and hyperactivity. The etiology of ADHD is not completely understood, but it is well known that the disorder has a moderate to high genetic component, with an estimated heritability of 76%. Polymorphic variants in several genes involved in regulation of the dopamine and related neurotransmitter pathways have been reported to be associated with ADHD. In this research we aimed to investigate the relationship between adult ADHD and DAT1 (dopamine transporter), DRD4 (dopamine D4 receptor), DRD3 (dopamine D3 receptor) gene polymorphisms.Method: Our study comprised unrelated 79 subjects who met DSM-IV criteria for adult ADHD and 75 controls and all were living in Denizli. All of the patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. With written informed consent, a blood sample was drawn from each subject individual. Venous blood samples were collected in ethylene diamine tetra acetic acid (EDTA) containing tubes. DNA was extracted from whole blood and genetic analyses were performed as described in the literature by using Polymerase Chain Reaction method. SSPSS 15.0 for Windows was used for statistical analyses.Results: Twenty-three of ADHD patients were defined as predominantly inattentive type, 22 of ADHD patients were defined as predominantly hyperactive-impulsive, and the rest of them were defined as combined type ADHD. 10/10 and 9/10 repeats were most relevant genotypes in both study and control group for DAT1 VNTR (variable number of tandem repeat) polymorphism. 4/4 and 4/7 repeats were mostly found in both study and control groups for DRD47- repeat allele gene polymorphism. Ser/Ser polymorphism was the most relevant genotype in both study and control group for DRD3 Ser9Gly gene polymorphism. DAT1 VNTR, DRD3 Ser9Gly, and DRD4 7- repeat allele gene polymorphisms were not associated with ADHD. These gene polymorphisms were also not associated with subtypes of ADHD.Conclusions: We couldn't detect any association between DAT1 VNTR, DRD3 Ser9Gly, and DRD4 7- repeat allele gene polymorphisms and adult ADHD. Ethnicity and sample size are important factors at case control type genetic studies. European studies mostly reported an association between polymorphism of these genes and ADHD, but majority of Middle Eastern and Asian studies didn't report such an association between these genes and ADHD. Multi centered future studies using genome wide scan and variable tandem repeat techniques with larger samples would be helpful for understanding the role of dopaminergic system at ADHD genetics

Receptor Gene Polymorphisms

Objective: Attention deficit hyperactivity disorder (ADHD) is a developmental disorder which is characterized by inattention, impulsiveness, and hyperactivity. The etiology of ADHD is not completely understood, but it is well known that the disorder has a moderate to high genetic component, with an estimated heritability of 76%. Polymorphic variants in several genes involved in regulation of the dopamine and related neurotransmitter pathways have been reported to be associated with ADHD. In this research we aimed to investigate the relationship between adult ADHD and DAT1 (dopamine transporter), DRD4 (dopamine D4 receptor), DRD3 (dopamine D3 receptor) gene polymorphisms.Method: Our study comprised unrelated 79 subjects who met DSM-IV criteria for adult ADHD and 75 controls and all were living in Denizli. All of the patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. With written informed consent, a blood sample was drawn from each subject individual. Venous blood samples were collected in ethylene diamine tetra acetic acid (EDTA) containing tubes. DNA was extracted from whole blood and genetic analyses were performed as described in the literature by using Polymerase Chain Reaction method. SSPSS 15.0 for Windows was used for statistical analyses.Results: Twenty-three of ADHD patients were defined as predominantly inattentive type, 22 of ADHD patients were defined as predominantly hyperactive-impulsive, and the rest of them were defined as combined type ADHD. 10/10 and 9/10 repeats were most relevant genotypes in both study and control group for DAT1 VNTR (variable number of tandem repeat) polymorphism. 4/4 and 4/7 repeats were mostly found in both study and control groups for DRD47- repeat allele gene polymorphism. Ser/Ser polymorphism was the most relevant genotype in both study and control group for DRD3 Ser9Gly gene polymorphism. DAT1 VNTR, DRD3 Ser9Gly, and DRD4 7- repeat allele gene polymorphisms were not associated with ADHD. These gene polymorphisms were also not associated with subtypes of ADHD.Conclusions: We couldn't detect any association between DAT1 VNTR, DRD3 Ser9Gly, and DRD4 7- repeat allele gene polymorphisms and adult ADHD. Ethnicity and sample size are important factors at case control type genetic studies. European studies mostly reported an association between polymorphism of these genes and ADHD, but majority of Middle Eastern and Asian studies didn't report such an association between these genes and ADHD. Multi centered future studies using genome wide scan and variable tandem repeat techniques with larger samples would be helpful for understanding the role of dopaminergic system at ADHD genetics

olanzapine in schizophrenia patients

Introduction: Genetic factors may influence response to antipsychotic treatment in patients with schizophrenia. The synaptosomal-associated protein of 25 kDa (SNAP-25) gene may be an interesting candidate gene regarding clinical outcome with antipsychotics. SNAP-25 is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters (1). Muller et al. reported that Mu1I T/G, Tail T/C polymorphisms in the SNAP-25 gene were associated with both antipsychotic drug response and drug induced weight gain (3). We aimed to evaluate the association of SNAP-25 (Mn1I T/G and Ddell T/C) polymorphisms with response to olanzapine in our study.Yontem: Our study comprised 86 unrelated subjects who strictly met DSM-IV criteria for schizophrenia and all were of Turkish origin. Genetic analyses were performed and patients were evaluated with rating scales.Results: When we compare the groups TT with TG+ GG patients with T/T genotype had better response to olanzapine for SANS scale in SNAP-25 Mn1I polymorphism. Also patients with TC+ CC genotype were responded better than patients with TT genotype for SNAP-25 Ddell polymorphism.Conclusion: Muller et al. reported that MnII and Tail polymorphisms (but not Ddel polymophism) were associated with response to olanzapine. Interestingly we found an association between SNAP-25 Ddell T/C polymorphism and response to olanzapine treatment. SNAP-25 gene polymorphisms might be related to antipsychotic response but further studies were needed

olanzapine in schizophrenia patients

Introduction: Genetic factors may influence response to antipsychotic treatment in patients with schizophrenia. The synaptosomal-associated protein of 25 kDa (SNAP-25) gene may be an interesting candidate gene regarding clinical outcome with antipsychotics. SNAP-25 is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters (1). Muller et al. reported that Mu1I T/G, Tail T/C polymorphisms in the SNAP-25 gene were associated with both antipsychotic drug response and drug induced weight gain (3). We aimed to evaluate the association of SNAP-25 (Mn1I T/G and Ddell T/C) polymorphisms with response to olanzapine in our study.Yontem: Our study comprised 86 unrelated subjects who strictly met DSM-IV criteria for schizophrenia and all were of Turkish origin. Genetic analyses were performed and patients were evaluated with rating scales.Results: When we compare the groups TT with TG+ GG patients with T/T genotype had better response to olanzapine for SANS scale in SNAP-25 Mn1I polymorphism. Also patients with TC+ CC genotype were responded better than patients with TT genotype for SNAP-25 Ddell polymorphism.Conclusion: Muller et al. reported that MnII and Tail polymorphisms (but not Ddel polymophism) were associated with response to olanzapine. Interestingly we found an association between SNAP-25 Ddell T/C polymorphism and response to olanzapine treatment. SNAP-25 gene polymorphisms might be related to antipsychotic response but further studies were needed

synaptosomal-associated protein (snap-25) polymorphisms

Introduction: The synaptosomal-associated protein of 25 kDa (SNAP-25) gene is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters (1). Previously, several studies reported association between SNAP-25 and attention deficit hyperactivity disorder (ADHD) (2). We investigated whether these SNAP-25 polymorphisms (Mn1I T/G and Ddell T/C) were also associated with ADHD in the Turkish population.Method: Our study comprised unrelated 79 subjects who met DSM-IV criteria for ADHD and 73 controls and all were of Turkish origin. Genetic analyses were performed and patients were evaluated with Wender-Utah and Turgay rating scales.Results: SNAP-25 Ddell polymorphism was not associated with ADHD but there was a statistically significant difference between ADHD patients and controls for SNAP-25 Mn1I polymorphism (p<0.05). For SNAP-25 Mn1I polymorphism patients with GG genotype had higher average of Wender-Utah and Turgay scores than patients with TT and TG genotype.Conclusion: We detected a significant association of the MnIl polymorphism in our ADHD sample which was similar to previous findings (2). Our study also revealed that SNAP-25 Mn1I polymorphism was also associated with symptom severity of ADHD. This study is also, the first report on the association of SNAP-25 with ADHD in the Turkish population