Genetic variation in ACE A2350G: association with reduction in fasting blood glucose after fluoxetine therapy in depressed patients

Various studies have shown that genetic factors contribute substantially to the development and progression of diabetes. Renin-angiotensin system has long been proven to have a major role in cardiovascular physiology and pathology. Its major product Angiotensin II (Ang II) with pro oxidant properties has shown to predict the future risk of diabetes. Fluoxetine, a drug of choice in management of depression, was observed to reduce fasting blood sugar (FBS). In the present study, six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 100newly diagnosed depressed individuals taking 12 weeks of fluoxetine. Blood samples were collected prior and after the period of treatment in order to measure FBS. Our results indicate that carriers of GG genotype of ACE A2350G showed significantly lower FBS levels after fluoxetine treatment (P=0.043). On the other hand haplotype analysis designate a significant association between DTG carriers of ACE I/D, A-240T and A2350G (P=0.001) and reduced FBS levels. In conclusion, this study supports the hypothesis that RAS genetic variations affect blood glucose after a course of treatment in Iranian population with depressio

ACE genetic variability and response to fluoxetine: lack of association in depressed patients

Evidences suggest that besides the neurotransmitters contributing to the development of depression, renin-angiotensin system (RAS) may also have a substantial role. Certain polymorphisms of RAS are associated with over activity of RAS &amp; depression. Considering that antidepressants reduce the actions of angiotensin II, the main product of RAS, this may come into mind that genetic polymorphisms of the mentioned system may affect the outcome of therapy in depressed patients.In the present study, 100 newly diagnosed depressed patients, according to DSM-IV criteria, were treated with 20 mg of fluoxetine for 8-12 weeks. Patients were categorized into responsive and non-responsive groups according to 50% reduction in symptoms. Genotype frequencies of angiotensin-converting enzyme (ACE) gene [ACE (I/D, A-240T and A2350G)] were then determined in DNAs extracted from venous blood of the patients using polymerase chain reaction–restriction fragment length polymorphism (PCR– RFLP) and PCR.Results indicate that polymorphisms studied and their haplotypes were not associated with better response to fluoxetine. However, a strong association between age and treatment in depressed Iranian patients was observed (P=0.001).In conclusion, unlike previous reports, this study does not support the hypothesis of special genotypes of RAS contributing to a better response to antidepressants in depressed patients.</p

Executive Functions among Traumatic Injury Patients: Comparison of Normal Individuals and those with Attention Deficit Hyperactivity Disorder

Objectives: To describe the executive function of patients with traumatic injury admitted to Rajaei hospital, Shiraz, Iran and to compare the executive function between normal individuals and those with Attention Deficit Hyperactivity Disorder (ADHD). Methods: This was a case control study being performed during a 6-month period during spring and summer of 2013 in Shiraz level I trauma center. We included all patients admitted during the study period with impression of traumatic injury with or without adult ADHD. The patients’ demographic factors were assessed through self-report questionnaire and executive functions by Wisconsin Card Sort Test (WCST) and Tower of London (TOL). Results were compared between normal individuals and those with ADHD. Results: Among 60 patients evaluated during the study period, with impression of traumatic injury, 29 fulfilled adult ADHD criteria and 31 were normal. The mean age of ADHD patients was 27.16±5.6 years and that of normal individuals was 26±3.4 years (p=0.330). There were no significant differences between two study groups regarding IQ (p=0.191) and education (p=0.396). Patients with ADHD had significantly poorer mean in executive functions in different parts of the test scoring system when compared to normal individuals. Conclusion: ADHD patients with traumatic injury had poor executive function compared to normal individuals. This might lead to poor inhibition, shifting and problem solving in this population

Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach

Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in the production of ATP, and the generation and management of reactive oxidative stress (ROS). This paper is a systematic review of the role of the mitochondrial electron transport chain in autism, and a consequent hypothesis for treating autism is synthesized.An electronic search with pre-specified inclusion criteria was conducted in order to retrieve all the published articles about the mitochondrial electron transport chain in autism. The two databases of PUBMED and Google Scholar were searched.From one hundred twenty five retrieved titles, 12 (three case control study and 9 case reports) articles met inclusion criteria. All of the included studies indicated dysfunction of electron transport chain in autism.The mitochondrial electron transfer chain seems impaired in some children with autism and ROS production is additionally enhanced. It is hypothesized that interventions involving alternative electron shuttling may improve autism through lowering the production of ROS. In addition, it is expected that this alternative electron shuttling to cytochrome c might enhance the production of ATP which is impaired in the disorder.</div

Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study.

BACKGROUND:Autism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism. METHODS:Considering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS:There were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64-5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37-3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26-2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008). CONCLUSION:Our data suggests the involvement of RAS genetic diversity in increasing the risk of autism

Comparison of haplotype frequencies in autistic patients and healthy individuals.

<p>Comparison of haplotype frequencies in autistic patients and healthy individuals.</p