SARS-CoV-2 reinfection rate before and after VOC Omicron emergence: a retrospective study in Brazil.

SARS-COV-2 reinfection has been reported worldwide, although its rate remains unclear. VOC Omicron's emergence and its sub-variants led to an unprecedented number of COVID-19 cases in several countries, raising concerns regarding reinfection rates. 324,979 RT-qPCR-confirmed positive cases (72.57% from Minas Gerais State) diagnosed between April 1, 2020, and August 31, 2022, at the Hermes Pardini, Grupo Fleury (Brazil) were used to estimate the reinfection rate. Instances of reinfection were characterized by two positive tests occurring with a minimum interval of 60 days. We identified 11,669 cases of reinfection. The states of Minas Gerais, São Paulo, Rio de Janeiro and Goiás represented almost 41% of the reinfections. Up until epidemiological week 46 of 2020, only 14 cases of reinfection were recorded. The majority of reinfections, totalling 6,316 cases, were detected during the circulation period of the Omicron and its sublineages BA.1 and BA.2. Another 4,273 reinfections occurred during the circulation period of sublineages BA.4 and BA.5, revealing two distinct groups of observations. The first group comprised cases of reinfection with a shorter time interval (two infections within a period of up to 200 days), while the second group was associated with a longer time interval (two infections within a period of more than 500 days). The reinfection rate during this period was nearly 8%, which is six times higher than the rate observed at the beginning of the study. In conclusion, our study underscores the dynamic nature of SARS-CoV-2 reinfections and their correlation with emerging variants such as Omicron.

Clinical, immunological, and microbiological analysis of the association between periodontitis and COVID-19: a case-control study.

PURPOSE: Periodontitis and coronavirus disease (COVID-19) share risk factors and activate similar immunopathological pathways, intensifying systemic inflammation. This study investigated the clinical, immunological and microbiological parameters in individuals with COVID-19 and controls, exploring whether periodontitis-driven inflammation contributes to worsening COVID-19 endpoints. METHODS: Case (positive RT-PCR for SARS-CoV-2) and control (negative RT-PCR) individuals underwent clinical and periodontal assessments. Salivary levels of TNF-α, IL-6, IL-1ß, IL-10, OPG, RANKL, neutrophil extracellular traps, and subgingival biofilm were analyzed at two timepoints. Data on COVID-19-related outcomes and comorbidity information were evaluated from medical records. RESULTS: Ninety-nine cases of COVID-19 and 182 controls were included for analysis. Periodontitis was associated with more hospitalization (p = 0.009), more days in the intensive care unit (ICU) (p = 0.042), admission to the semi-ICU (p = 0.047), and greater need for oxygen therapy (p = 0.042). After adjustment for confounders, periodontitis resulted in a 1.13-fold increase in the chance of hospitalization. Salivary IL-6 levels (p = 0.010) were increased in individuals with COVID-19 and periodontitis. Periodontitis was associated with increased RANKL and IL-1ß after COVID-19. No significant changes were observed in the bacterial loads of the periodontopathogens Porphyromona gingivalis, Aggregatibacter actinomycetemcomitans, Tanerella forsythia, and Treponema denticola. CONCLUSIONS: Periodontitis was associated with worse COVID-19 outcomes, suggesting the relevance of periodontal care to reduce the burden of overall inflammation. Understanding the crosstalk between SARS-CoV-2 infection and chronic conditions such as periodontitis that can influence disease outcome is important to potentially prevent complications of COVID-19.

Influence of polymorphisms in CYP2C9, VKORC1, MDR1 and APOE genes on the warfarin maintenance dose in Brazilian patients.

Background: Polymorphisms in the CYP2C9, VKORC1, MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic, clinical factors and polymorphisms *1, *2 and *3 for CYP2C9, -1639G>A for VKORC1, 3435C>T for MDR1, and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.

Association of 3p21.31 Locus (CXCR6 and LZTFL1) with COVID-19 Outcomes in Brazilian Hospitalyzed Subjects.

The 3p21.31 locus has been associated with severe COVID-19 prognosis in GWAS studies. Here, we evaluated whether three polymorphisms (LZTFL1 rs10490770, CXCR6 rs2234355 and rs2234358) in the reported locus were associated with the need for mechanical ventilation, hospitalization length and death in 102 COVID-19 hospitalized Brazilian subjects. No genetic association was found with the need for mechanical ventilation and hospitalization length. CXCR6 rs2234355 was associated with mortality under the codominance model, with carriers of the A/A genotype having a greater chance of death than A/G (OR: 10.5; 95% CI: 1.55-70.76). Our results further suggest that the CXCR6 genetic variant contributes to COVID-19 outcomes.

Can SARS-CoV-2 screening in oral biopsies aid epidemiological surveillance?

BACKGROUND: Three years after the first confirmed COVID-19 case in Brazil, the outcomes of Federal government omissions in managing the crisis and anti-science stance heading into the pandemic have become even more evident. With over 36 million confirmed cases and nearly 700 000 deaths up to January 2023, the country is one of the hardest-hit places in the world. The lack of mass-testing programs was a critical broken pillar responsible for the quick and uncontrolled SARS-CoV-2 spread throughout the Brazilian population. Faced with this situation, we aimed to perform the routine SARS-CoV-2 screening through RT-qPCR of oral biopsies samples to aid in the asymptomatic epidemiological surveillance during the principal outbreak periods. METHODS: We analyzed 649 formalin-fixed paraffin-embedded oral tissue samples from five important oral and maxillofacial pathology laboratories from the north, northeast, and southeast geographic regions of Brazil. We also sequenced the whole viral genome of positive cases to investigate SARS-CoV-2 variants. RESULTS: The virus was detected in 9/649 analyzed samples, of which three harbored the Variant of Concern Alpha (B.1.1.7). CONCLUSION: Although our approach did not value aiding asymptomatic epidemiological surveillance, we could successfully identify a using FFPE tissue samples. Therefore, we suggest using FFPE tissue samples from patients who have confirmed diagnosis of SARS-CoV-2 infection for phylogenetic reconstruction and contraindicate the routine laboratory screening of these samples as a tool for asymptomatic epidemiological surveillance.

Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders.

In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.

SARS-CoV-2 Omicron BA.1, BA.2, and XAG identification during routine surveillance on a university campus in Belo Horizonte, Brazil, 2022.

We report SARS-CoV-2 genomic surveillance results between Belo Horizonte, Brazil's third and fourth case waves. Samples were obtained through a routine university monitoring COVID-19 program from the 9th to the 22nd epidemiological weeks (March and June 2022). We identified ten samples from the BA.1 clade (BA.1, BA.1.1, and BA.1.14.1 lineages) and 45 samples from the BA.2 clade (BA.2, BA.2.56, BA.2.9, BA.2.62, BA.2.23, BA.2.81, and BA.2.10). We observed progressive replacement of the BA.1 by the BA.2 clade. Furthermore, two XAG recombinants were found in the 22nd week. Diversification of the omicron variant seems to have contributed to the resurgence of cases in Belo Horizonte, similarly to what has been reported in South Africa.

Persistent symptoms, quality of life, and risk factors in long COVID: a cross-sectional study of hospitalized patients in Brazil.

OBJECTIVES: COVID-19 has been associated with long-term consequences to patient wellness and quality of life. Data on post-COVID-19 conditions are scarce in developing countries. This study aimed to investigate long COVID in a cohort of hospitalized patients in Brazil. METHODS: Surviving patients discharged from the hospital between July 1, 2020 and March 31, 2021 were assessed between 2 and 12 months after acute onset of COVID-19. The outcomes were the prevalence of persistent symptoms, risk factors associated with long COVID, and quality of life as assessed by the EuroQol 5D-3L questionnaire. RESULTS: Of 439 participants, most (84%) reported at least one long COVID symptom, at a median of 138 days (interquartile range [IQR] 90-201) after disease onset. Fatigue (63.1%), dyspnea (53.7%), arthralgia (56.1%), and depression/anxiety (55.1%) were the most prevalent symptoms. In multivariate analysis, dysgeusia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.18-3.44, P <0.001) and intensive care unit (ICU) admission (OR 2.6, 95% CI 1.19-6.56, P = 0.03) were independently associated with long COVID. Fifty percent of patients reported a worsened clinical condition and quality of life. CONCLUSION: Long-term outcomes of SARS-CoV-2 infection in a low- to middle-income country were relevant. Fatigue was the most common persistent symptom. ICU admission was an independent factor associated with long COVID. Dysgeusia could be a potential predictor of long COVID.

Biosafety in Dental Health Care During the COVID-19 Pandemic: A Longitudinal Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic had quite an impact on dental health care. Concerns about the risk of SARS-CoV-2 transmission through contaminant fluids and droplet formation during several dental procedures highly impacted dental health care, drastically reducing the number of dental practices worldwide. To monitor SARS-CoV-2 contamination in dental clinics, a longitudinal study was carried out during the return of dental practice at university. Methods: Dental health care professionals [(DHCPs); teachers, undergraduate dental students, and dental assistants] and patients were screened for SARS-CoV-2 RNA in a dental school clinic environment from 11th January to 12th March 2021 (9 weeks). Serological testing was performed on DHCPs in two-time points. Additionally, samples with low Ct values were sequenced to identify the circulating SARS-CoV-2 variant and possible transmission clusters. Results: We found a low number of dental staff (5.8%), patients (0.9%), and environment sites (0.8%) positive for SARS-CoV-2. Most positive cases had asymptomatic to mild symptoms, and two asymptomatic DHCPs presented prolonged infection. In the first week after previous exposure to COVID-19, 16.2% of DHCPs had IgM or IgG antibodies against SARS-CoV-2, and 1/3 of them had undetected antibodies in the last weeks. The variant zeta (P.2) could be detected. No cross-infection was observed between participants. Conclusion: Our study suggests that dental practice can be safely executed when adequate control measures and biosafety protocols are applied. DHCP and patient testing, patient telemonitoring, proper use of personal protection equipment, and sanitization of surfaces are essential to avoid SARS-CoV-2 cross-infection in dental practice.

IFITM3, FURIN, ACE1, and TNF-α Genetic Association With COVID-19 Outcomes: Systematic Review and Meta-Analysis.

Human polymorphisms may contribute to SARS-CoV-2 infection susceptibility and COVID-19 outcomes (asymptomatic presentation, severe COVID-19, death). We aimed to evaluate the association of IFITM3, FURIN, ACE1, and TNF-α genetic variants with both phenotypes using meta-analysis. The bibliographic search was conducted on the PubMed and Scielo databases covering reports published until February 8, 2022. Two independent researchers examined the study quality using the Q-Genie tool. Using the Mantel-Haenszel weighted means method, odds ratios were combined under both fixed- and random-effect models. Twenty-seven studies were included in the systematic review (five with IFITM3, two with Furin, three with TNF-α, and 17 with ACE1) and 22 in the meta-analysis (IFITM3 n = 3, TNF-α, and ACE1 n = 16). Meta-analysis indicated no association of 1) ACE1 rs4646994 and susceptibility, 2) ACE1 rs4646994 and asymptomatic COVID-19, 3) IFITM3 rs12252 and ICU hospitalization, and 4) TNF-α rs1800629 and death. On the other hand, significant results were found for ACE1 rs4646994 association with COVID-19 severity (11 studies, 692 severe cases, and 1,433 nonsevere controls). The ACE1 rs4646994 deletion allele showed increased odds for severe manifestation (OR: 1.45; 95% CI: 1.26-1.66). The homozygous deletion was a risk factor (OR: 1.49, 95% CI: 1.22-1.83), while homozygous insertion presented a protective effect (OR: 0.57, 95% CI: 0.45-0.74). Further reports are needed to verify this effect on populations with different ethnic backgrounds. Systematic Review Registration: https://www.crd.york.ac.uk/prosperodisplay_record.php?ID=CRD42021268578, identifier CRD42021268578.

Seroprevalence, Prevalence, and Genomic Surveillance: Monitoring the Initial Phases of the SARS-CoV-2 Pandemic in Betim, Brazil.

The COVID-19 pandemic has created an unprecedented need for epidemiological monitoring using diverse strategies. We conducted a project combining prevalence, seroprevalence, and genomic surveillance approaches to describe the initial pandemic stages in Betim City, Brazil. We collected 3239 subjects in a population-based age-, sex- and neighborhood-stratified, household, prospective; cross-sectional study divided into three surveys 21 days apart sampling the same geographical area. In the first survey, overall prevalence (participants positive in serological or molecular tests) reached 0.46% (90% CI 0.12-0.80%), followed by 2.69% (90% CI 1.88-3.49%) in the second survey and 6.67% (90% CI 5.42-7.92%) in the third. The underreporting reached 11, 19.6, and 20.4 times in each survey. We observed increased odds to test positive in females compared to males (OR 1.88 95% CI 1.25-2.82), while the single best predictor for positivity was ageusia/anosmia (OR 8.12, 95% CI 4.72-13.98). Thirty-five SARS-CoV-2 genomes were sequenced, of which 18 were classified as lineage B.1.1.28, while 17 were B.1.1.33. Multiple independent viral introductions were observed. Integration of multiple epidemiological strategies was able to adequately describe COVID-19 dispersion in the city. Presented results have helped local government authorities to guide pandemic management.

Effects of aging on DNA hydroxymethylation and methylation in human dental follicles.

OBJECTIVE: Despite the high frequency of impacted teeth and increased frequency of lesions in dental follicles (DF) with aging, DF age-changes remain unclear. We compared the global methylation and hydroxymethylation profiles in DF in relation to age. DESIGN: DF associated with impacted lower third molars were obtained from 59 individuals. Global DNA methylation (5mC content) and hydroxymethylation (5hmC) were evaluated by ELISA. We tested the correlation between 5mC and 5hmC content, and the correlation of each with patients' age. The differences in age, 5mC, and 5hmC in DF from men/women, and location (left/right mandible) was tested. RESULTS: The mean age of the 59 individuals was 19.56 ±â€¯3.92, ranging from 13 to 31 years, and most were women (n = 39). 5hmC content and age up to 19 years were inversely correlated (Spearman's correlation coefficient=-0.552, p = 0.0003, n = 38). There was no relationship between 5hmC and 5mC content. There was no difference in the medians of age (p = 0.25), 5hmC (p = 0.33) and 5mC (p = 0.86) between men/women, nor in the medians of age (p = 0.39), 5hmC (p = 0.99) and 5mC (p = 0.22) between the left/right side of the tooth extraction. CONCLUSION: An inverse correlation between 5hmC and age was established, with no correlation between 5mC and 5hmC content in DF. The biological meaning of such a decrease of global DNA hydroxymethylation with age in DF remains to be clarified.

Early postnatal l-Dopa treatment causes behavioral alterations in female vs. male young adult Swiss mice.

Dopaminergic signaling and neurodevelopment alterations are associated with several neuropsychiatric disorders. Knockout mice for dopamine transporters (DAT) as well as site-specific knockout mice lacking dopaminergic D2 autoreceptors in dopaminergic neurons (DA-D2RKO) display behavioral alterations such as hyperlocomotion and abnormal prepulse inhibition. However, it is possible that dopaminergic imbalances may have different effects during varied neurodevelopmental windows. In our previous study, we observed that elevated levels of dopamine during the perinatal developmental window increased exploratory behavior of juvenile (4-week-old) Swiss female mice and impaired hedonic behavior in males. In this study, we investigated whether these behavioral alterations persist through young adulthood. In order to do so, we administered daily doses of l-Dopa to mice pups beginning from postnatal day 1 (PD1) to PD5. At the age of 8 weeks, we submitted the young adult males and females to the open field test, elevated plus maze, forced swimming test, and sucrose preference test. We observed that augmentation of dopamine levels during the perinatal developmental window increased locomotor behavior in females, but not males. We also observed an increase in anxiety-behavior in females and anxiolytic-like behavior in males. In addition, we observed stress-coping behavior in males and an increase of hedonic behavior in females. Our results show that dopamine signaling is important for behavioral development and that transient imbalances of dopamine levels can cause permanent behavioral alterations - alterations which are different in males than in females. These data may help in better understanding the spectrum of symptoms associated with different neuropsychiatric disorders.

Behavioral plasticity and gene regulation in the brain during an intermittent ethanol exposure in adult zebrafish population.

Ethanol consumption is correlated with different neurobiological and behavioral impairments. Acute and chronic exposure to this drug is associated with alterations in the regulation of the mesolimbic dopaminergic system as well as with transcriptional modulation of other receptors in the central nervous system and can unleash seeking behavior or behavioral adaptations and phenotypes such as loss of control, dependence and tolerance. In the present work, we characterized the chronological effects of acute and chronic intermittent exposure to ethanol (1% v/v) in an adult zebrafish population (Danio rerio). During sixteen days of ethanol exposure, we associated the neuromodulation of target genes (drd1, drd2, gabra2a, gabbr1a, gabbr1b) in the central nervous system with behavioral parameters, assessed by social preference, antipredatory capacity and anxiety-like analysis. Transcriptional and behavioral data were collected in days 0, 1, 4, 8, 12 and 16, after ethanol exposure. In days 1 and 4, ethanol exposure increased exploratory behavior regardless of the risk involved (less time spent close to conspecifics and lower avoidance reaction to predator). Along with the reduction of drd2, grin1a and gabra2a transcription seen in the same days, these results suggest an anxiolytic effect of acute ethanol exposure. Interestingly, in days 8, 12 and 16, an attenuation of the behavioral effects was observed. The social preference, antipredatory behavior, perception and exploration parameters were reconstituted. This behavioral re-establishment, accompanied by the increase in drd1, drd2 and gabbr1a transcription in the 8th day could be an indicative of an adaptation to chronic exposure to ethanol. The modulation of drd2 gene combined with the behavioral characterization observed in the study suggests this signalling pathway as a key participant in the phenotypic outcomes of a long-term chronic exposure to ethanol. Lastly, our results reaffirm the ethanol deleterious impacts in perception, ability to respond to adverse stimuli and in anxiety-like behavior.

Disentangling the Environmental Factors That Shape Genetic and Phenotypic Leaf Trait Variation in the Tree Qualea grandiflora Across the Brazilian Savanna.

Identifying the environmental factors that shape intraspecific genetic and phenotypic diversity of species can provide insights into the processes that generate and maintain divergence in highly diverse biomes such as the savannas of the Neotropics. Here, we sampled Qualea grandiflora, the most widely distributed tree species in the Cerrado, a large Neotropical savanna. We analyzed genetic variation with microsatellite markers in 23 populations (418 individuals) and phenotypic variation of 10 metamer traits (internode, petiole and corresponding leaf lamina) in 36 populations (744 individuals). To evaluate the role of geography, soil, climate, and wind speed in shaping the divergence of genetic and phenotypic traits among populations, we used Generalized Dissimilarity Modelling. We also used multiple regressions to further investigate the contributions of those environmental factors on leaf trait diversity. We found high genetic diversity, which was geographically structured. Geographic distance was the main factor shaping genetic divergence in Qualea grandiflora, reflecting isolation by distance. Genetic structure was more related to past climatic changes than to the current climate. We also found high metamer trait variation, which seemed largely influenced by precipitation, soil bulk density and wind speed during the period of metamer development. The high degree of metamer trait variation seems to be due to both, phenotypic plasticity and local adaptation to different environmental conditions, and may explain the success of the species in occupying all the Cerrado biome.

Does cell phone use increase the chances of parotid gland tumor development? A systematic review and meta-analysis.

BACKGROUND: Prior epidemiological studies had examined the association between cell phone use and the development of tumors in the parotid glands. However, there is no consensus about the question of whether cell phone use is associated with increased risk of tumors in the parotid glands. We performed a meta-analysis to evaluate the existing literature about the mean question and to determine their statistical significance. METHODS: Primary association studies. Papers that associated cell phone use and parotid gland tumors development were included, with no restrictions regarding publication date, language, and place of publication. Systematic literature search using PubMed, SciELO and Embase followed by meta-analysis. RESULTS AND CONCLUSION: Initial screening included 37 articles, and three were included in meta-analysis. Using three independent samples including 5087 subjects from retrospective case-control studies, cell phone use seems to be associated with greater odds (1.28, 95%- confidence interval: 1.09-1.51) to develop salivary gland tumor. Results should be read with caution due to the limited number of studies available and their retrospective design.

Association between DCHS2 gene and mild cognitive impairment and Alzheimer's disease in an elderly Brazilian sample.

OBJECTIVES: In 2012, Kamboh and colleagues published a genome-wide association study that identified the DCHS2 gene (rs1466662 T/A) influencing the age at onset of Alzheimer's disease (AD). We aimed to investigate if there is association between the DCHS2 gene and amnestic mild cognitive impairment (aMCI) and AD in a sample of the Brazilian population. METHODS: 143 controls, 79 aMCI and 299 AD patients were selected and submitted to the same protocol of tests. Genotyping was performed using the Real Time PCR RESULTS: Amnestic MCI patients showed a higher prevalence of AA than controls and a lower frequency of TT when compared with controls. We also stratified the sample according to the APOE ε4 status. No difference in DCHS2 genotype or allelic frequency occurred in the APOE ε4 allele carrier subgroup. Amnestic MCI patients showed a higher frequency of AA genotype and a lower frequency of TA and TT when compared with controls in APOE ε4 allele non-carrier subgroup. The allelic distribution followed the same pattern. In AD group, we observed a significant difference with a higher A allelic frequency in AD in this subgroup. A multiple logistic regression demonstrated that in APOE ε4 non-carriers, allele rs1466662 was associated to aMCI group. Different variables were associated with aMCI and AD according to APOE ε4 status in our sample. Low level of education was associated with AD, while diabetes mellitus type 2 was associated with aMCI. Copyright © 2016 John Wiley & Sons, Ltd. CONCLUSIONS: Our findings suggest a possible role for DCHS2 gene in aMCI and AD.