Patricia Araújo Pereira

Homozygosity for the +674C>T polymorphism on VEGF gene is associated with age-related macular degeneration in a Brazilian cohort

PurposeTo investigate the association between VEGF gene polymorphism and age-related macular degeneration (AMD) in a Brazilian cohort.MethodsWe examined 160 affected individuals and 140 sex- and age-matched controls recruited at the Vision Institute and the Retina Department, São Geraldo Hospital, Minas Gerais Federal University, Brazil, between 2007 and 2011. Genotyping for the VEGF rs1413711 single nucleotide polymorphism (SNP) (+674C>T) was performed. The incidence rate ratios and 95% confidence interval (CI) for AMD for this genotype was calculated. The odds ratio (OR) was also assessed by using logistic regression, controlling for CFH and LOC387715 risk genotype.ResultsWe observed a prevalence of homozygosity (TT genotype) of 18.1% for rs1413711 among AMD cases compared with 5.8% among controls (P < 0.002). The ORs for this polymorphism were 3.6 (95%CI 1.6–8.2) for homozygous subjects and 1.5 (95%CI 1.1–2.1, P < 0.01) if the subject had at least one risk allele. When we studied separately exudative and dry AMD groups, this polymorphism was statistically significant for both groups. Controlling for CFH and LOC387715 risk genotype the OR was 3.0 for VEGF homozygous, and the OR increases if the patient is homozygous for the three genes.ConclusionThe present data suggests that VEGF TT genotype is associated with AMD among Brazilian patients.

Association of polymorphisms of the tryptophan hydroxylase 2 gene with risk for bipolar disorder or suicidal behavior

Bipolar disorder (BD) is a severe psychiatric illness characterized by the occurrence of elevated mood alternating with depressive episodes, having a estimated lifetime prevalence of 0.4-1.6% using DSM-IV criteria. Disturbances of the central serotonergic system has been associated with the pathophysiology of affective disorders and suicidal behavior. Tryptophan hydroxylase 2 (TPH2) which is a rate limiting enzyme in the serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. Our sample consisted of 527 subjects (303 diagnosed with bipolar disorder and 224 healthy controls) which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the whole gene of the human TPH2. Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview((R)). Single markers, genotype and haplotype association analysis did not show significant genetic association with bipolar disorder or suicidal behavior. Our findings do not support the association between diagnosis of BD or suicidal behavior and TPH2 polymorphisms.

Association study of tryptophan hydroxylase 2 gene polymorphisms in bipolar disorder patients with panic disorder comorbidity

Frequent comorbidity between panic disorder (PD) and mood disorders has been widely reported in clinical and epidemiological studies and, recently, an increasing attention has been paid to the cooccurrence of PD and bipolar disorder (BD). Several studies have shown that an imbalance of serotonin activity could be related to panic symptoms. Tryptophan hydroxylase 2 (TPH2) are plausible candidates for the association with PD. The aim of this study is to investigate a possible association between TPH2 gene polymorphisms and the PD comorbidity susceptibility.Our sample consisted of 515 patients; 274 patients with BD (subtypes I and II), including 45 patients with lifetime panic disorder comorbidity and 241 controls. These patients were genotyped for eight tagging single nucleotide polymorphisms of the gene of human TPH2. We found significant differences between patients with BD, with panic disorder comorbidity, and controls in the allelic analysis (rs4448731, P=0.0069; rs4565946, P=0.0359; rs4760820, P=0.0079; rs1487275, P=0.0439) and genotypic analysis (rs4448731, P=0.011; rs4760820, P=0.0259). We also identified significant differences between patients with BD, with and without panic disorder comorbidity in the allelic analysis (rs4448731, P=0.004; rs4565946, P=0.011; rs11179000, P=0.031; rs4760820, P=0.018; rs1487275, P=0.038; rs10879357, P=0.023) and genotypic analysis (rs4448731, P=0.004; rs4565946, P=0.010; rs4760820, P=0.023; rs10879357, P=0.052). The haplotype analysis in the group of patients with BD, with and without panic disorder comorbidity, was also significant (rs4448731-rs4565946, P=0.0190; rs4448731-rs4565946, P=0.0220; rs10506645-rs4760820, P=0.0360). Further studies are needed to replicate the positive association that we observed.

Increased frequency of T cells expressing IL-10 in Alzheimer disease but not in late-onset depression patients.

Higher risk of dementia is expected for patients with late onset depression (LOD) history. The IL-10 polymorphisms are associated with Alzheimer disease (AD). On the other hand, there is no study associating IL-10 polymorphisms to LOD. This study aimed to investigate the -1082G/A polymorphism association in LOD, AD patients and controls and also the peripheral expression of IL-10 in CD4+ T cells. It was done in a case-control study comparing immune system phenotype and genetic polymorphism association among control individuals, LOD and AD patients. Participants were 569 subjects composed the genetics sample (249 AD, 222 LOD and 98 controls) from a tertiary medical center based on Belo Horizonte, Brazil. Flow cytometry analysis was performed in 55 people (22 AD patients, 11 LOD patients and 22 controls). A real time PCR for IL-10 SNP (rs 1800896) through genotyping analysis and flow cytometry evaluation of CD4+ T cells expressing IL-10 was done. An increased CD4+ T cells expressing IL-10 were detected only in the AD group. There was no difference detected in allele or genotype analysis for IL-10 polymorphism among LOD, AD patients or controls. IL-10 might have a role in the modulation of immune response in AD patients, however it is not presented in LOD population.

Association Between Tryptophan Hydroxylase-2 Gene and Late-Onset Depression

OBJECTIVE The aim of this study was to examine the association between polymorphisms (SNP) in the tryptophan hydroxylase-2 (TPH2) gene and late-onset depression (LOD) in the Brazilian population. METHODS We genotyped 8 tag SNPs in the TPH2 gene in 84 outpatients with LOD and 79 individuals belonging to the comparison group to investigate an association between the TPH2 gene and LOD. RESULTS Our findings suggested an association between tag SNP rs4565946 heterozygous C/T (p = 0.034; χ2 = 6.7; df = 2) and decreased risk of LOD. The tag SNP rs11179000 ancestral homozygous A/A (p = 0.025; χ2 = 7.3; df = 2) and increase risk of LOD and allelic association of ancestral allele A and increase risk of LOD was demonstrated (p = 0.005; χ2 = 7.8; df = 1). CONCLUSION We found the statistically significant association between two tag SNPs and LOD. Our results support the hypothesis that the TPH2 gene is associated with LOD.

Catechol-O-Methyltransferase GeneticVariant Associated with the Risk of Alzheimer’s Disease in a Brazilian Population

The aim of the present study was to examinethe association between polymorphism in thecatechol-O-methyltransferase(COMT) gene and Alzheimer’s disease (AD) in a Brazilianpopulation. The case-control method was used to study the association between AD and geneticvariants of COMT. Six tag single-nucleotide polymorphisms(SNPs) in the COMT gene were genotyped by RT-PCR. Ourfindings showed that the 6 tag SNPs analyzed in this study were not associated with AD at the alleleand genotype levels in comparison with the control group. No statistical difference was foundbetween groups with and without behavioral and psychological symptoms of dementia (BPSD). Ourresults do not support the hypothesis that the polymorphisms of theCOMT gene may be associated with susceptibility to AD withand without BPSD.

Genetic variant of AKT1 and AKTIP associated with late-onset depression in a Brazilian population

Examine the association between polymorphisms in the AKT1 and AKTIP genes and late‐onset depression (LOD). Major depressive disorder is one of the most prevalent neuropsychiatric diseases. LOD is a disorder that starts after 65 years old. AKT1 is a downstream enzyme that has been implicated in the pathogenesis of neurotransmitter‐related disorders, such as depression. The identification of a novel AKT1‐binding protein (AKTIP) was pointed as an important new target. AKTIP binds directly to AKT1, enhancing the phosphorylation of regulatory sites, and this modulation are affected by AKT1 activation. The association of AKT1 and AKTIP polymorphisms with depressive symptoms was not investigated in LOD.

Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease

Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia.

Increased frequency of cluster of differentiation 14 (CD14+) monocytes expressing interleukin 1 beta (IL-1β) in Alzheimer's disease patients and intermediate levels in late-onset depression patients.

Depression might be a prodromal stage of dementia. Many factors contribute to the etiology of depression and dementia, being inflammation one of those. The present work measured and analyzed immune molecules involved in the innate immunity on cluster of differentiation 14 (CD14+) monocytes trying to investigate any relationship among late‐onset depression (LOD) and Alzheimers disease (AD).

Lack of association between genetic polymorphism of FTO, AKT1 and AKTIP in childhood overweight and obesity

OBJECTIVE Obesity is a chronic disease caused by both environmental and genetic factors. Epidemiological studies have documented that increased energy intake and sedentary lifestyle, as well as a genetic contribution, are forces behind the obesity epidemic. Knowledge about the interaction between genetic and environmental components can facilitate the choice of the most effective and specific measures for the prevention of obesity. The aim of this study was to assess the association between the FTO, AKT1, and AKTIP genes and childhood obesity and insulin resistance. METHODS This was a case-control study in which SNPs in the FTO (rs99396096), AKT1, and AKTIP genes were genotyped in groups of controls and obese/overweight children. The study included 195 obese/overweight children and 153 control subjects. RESULTS As expected, the obese/overweight group subjects had higher body mass index, higher fasting glucose, HOMA-IR index, total cholesterol, low-density lipoprotein, and triglycerides. However, no significant differences were observed in genes polymorphisms genotype or allele frequencies. CONCLUSION The present results suggest that AKT1, FTO, and AKTIP polymorphisms were not associated with obesity/overweight in Brazilians children. Future studies on the genetics of obesity in Brazilian children and their environment interactions are needed.