Epidemiology of the SARS-CoV-2 Omicron Variant Emergence in the Southeast Brazilian Population.

The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants' lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0-10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron's sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.

Identification of four novel HLA alleles: HLA-B*27:265, -B*35:569, -DRB1*08:117 and -DPB1*1435:01.

Identification of four new HLA alleles (B*27:265, B*35:569, DRB1*08:117, and DPB1*1435:01) in Brazilian bone marrow donors.

Interlocus gene conversion: Identification of HLA-A*23:128 in a Brazilian bone marrow donor.

Identification of novel HLA-A*23:128 allele generated by interlocus gene conversion in Brazilian bone marrow donor.

CCR5 promoter region polymorphisms in systemic lupus erythematosus.

This study investigated the impacts of CCR5 promoter region polymorphisms on the development of systemic lupus erythematosus (SLE) by comparing CCR5 genotypes and haplotypes from SLE patients with ethnically matched controls. A total of 382 SLE patients (289 European-derived and 93 African-derived) and 375 controls (243 European-derived and 132 African-derived) were genotyped for the CCR2-64I G > A (rs1799864), CCR5-59353 C > T (rs1799988), CCR5-59356 C > T (rs41469351), CCR5-59402 A > G (rs1800023) and CCR5-59653 C > T (rs1800024) polymorphisms through polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Previous data from CCR5Δ32 analysis was included in the study to infer the CCR5 haplotypes and as a possible confounding factor in the binary logistic regression. European-derived patients showed a higher frequency of CCR5 wild-type genotype (conversely, a reduced frequency of Δ32 allele) and a reduced frequency of the HHG*2 haplotype compared to controls; both factors significantly affecting disease risk [p = .003 (OR 3.5, 95%CI 1.6-7.5) and 2.0% vs. 7.2% (residual p = 2.9E - 5), respectively]. Additionally, the HHA/HHB, HHC and HHG*2 haplotype frequencies differed between African-derived patients and controls [10% vs. 20.5% (residual p = .003), 29.4% vs. 17.4% (residual p = .003) and 3.9% vs. 0.8% (residual p = .023), respectively]. Considering the clinical manifestations of the disease, the CCR5Δ32 presence was confirmed as a susceptibility factor to class IV nephritis in the African-derived group and when all patients were grouped for comparison [pcorrected  = .012 (OR 3.0; 95%CI 3.0-333.3) and pcorrected  = .0006 (OR 6.8; 95%CI 1.9-24.8), respectively]. In conclusion, this study indicates that CCR5 promoter polymorphisms are important disease modifiers in SLE. Present data reinforces the CCR5Δ32 polymorphism as a protective factor for the development of the disease in European-derived patients and as a susceptibility factor for class IV nephritis in African-derived patients. Furthermore, we also described a reduced frequency of HHA/HHB and an increased frequency of HHC and HHG*2 haplotypes in African-derived patients, which could modify the CCR5 protein expression in specific cell subsets.

Epidemiology of the SARS-CoV-2 Omicron variant emergence in the Southeast Brazilian population

The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants’ lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0–10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron’s sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.

Analysis of 12 X-STRs loci in a population from southeastern Brazil.

Short tandem repeat (STR) markers on the X chromosome have a high potential for solving complex kinship analysis and individual identification cases. To achieve such purposes, allele and haplotype frequencies for the specific population are necessary. Nonetheless, such frequencies are not always available. Therefore, we obtained haplotypes from 520 unrelated males from four different geographic regions of Espírito Santo - Brazil, using the Investigator Argus X-12 kit. Forensic parameters for linked groups of four X-STR loci are reported. Genetic distance analyzes suggest that ES population is genetically closer to the Italian population and farther from the Mexican one, among the populations analyzed in this study.

Lack of association between month of birth and risk of developing type 1 diabetes in Brazil: a 40-year analysis.

OBJECTIVES: Seasonal environment at birth may influence diabetes incidence in later life. We sought evidence for this effect and analyzed the association between the month of birth and the risk of developing type 1 diabetes mellitus (T1DM). METHODS: This was a cohort study carried out with 814 patients diagnosed with T1DM in the region of Bauru - São Paulo State, Brazil, receiving medical care in a private Endocrinology clinic or in the public Brazilian National Health Care System, from 1981 to 2021. All live births that occurred in São Paulo State between 1974 and 2020 were classified by month of birth and were considered as the control group. RESULTS: We found no statistically significant difference (χ2=16.31, critical 19.68) between the month of birth and risk of developing T1DM, when comparing our patients with the background population of the region. There was no association between the month of birth, sex, age at diagnosis, duration of symptoms before diagnosis, self-reported color, and socioeconomic status. CONCLUSIONS: We found no association between month of birth and the risk of developing T1DM in this highly admixed South American population. Our data suggest that our population heterogeneity and geographic location may be important factors in the development of T1DM. Future prospective studies, evaluating environmental factors that may confer risk or protection to the disease, are warranted.

Association between Dietary Inflammatory Index and Gastric Adenocarcinoma: A Multicenter Case-Control Study in Brazil.

BACKGROUND: Few studies have evaluated the association between diet-related inflammation and gastric adenocarcinoma (GA) and evidence is scarce in Brazil. This study evaluated the association between a pro-inflammatory diet and GA. METHODS: A multicenter case-control study was conducted in Brazil. A total of 1645 participants-492 cases, 377 endoscopy controls, and 776 hospital controls-were included. Energy-adjusted Dietary Inflammatory Index (E-DIITM) scores were derived from a validated food frequency questionnaire. We used binary and multinomial logistic regression models for the analysis of total GA, and its subtypes (cardia and non-cardia, intestinal, and diffuse histological subtypes). RESULTS: In cases versus endoscopy controls, a pro-inflammatory diet, estimated by higher E-DII scores, was associated with a higher risk GA (ORQ4vsQ1: 2.60, 1.16-5.70), of non-cardia GA (OR: 2.90, 1.06-7.82), and diffuse subtype (OR: 3.93, 1.59-9.70). In cases versus hospital controls, higher E-DII scores were associated with a higher risk of GA (OR: 2.70, 1.60-4.54), of cardia GA (OR: 3.31, 1.32-8.24), non-cardia GA (OR: 2.97, 1.64-5.39), and both intestinal (OR: 2.82, 1.38-5.74) and diffuse GA (OR: 2.50, 1.54-5.11) subtypes. CONCLUSIONS: This study provides evidence that a pro-inflammatory diet is associated with an increased risk of GA in Brazil. E-DII requires the inclusion of sodium due to its importance in carcinogenesis.

Allele Frequencies and Forensic Data of 25 STR Markers for Individuals in Northeast Brazil.

Identifying DNA markers such as Short Tandem Repeats (STR) can be used to investigate genetic diversity based on levels of heterozygosity within and between populations. Allele frequencies and forensic data for STRs were obtained from a sample of 384 unrelated individuals living in Bahia, Northeastern Brazil. Thus, the present study aimed to identify the allele frequency distribution, in addition to the forensic and genetic data, of 25 STR loci in the population of Bahia. Buccal swabs or fingertip punctures were utilized to amplify and detect 25 DNA markers. The most polymorphic loci were SE33 (43), D21S11, and FGA (21). The least polymorphic were TH01 (6), TPOX, and D3S1358 (7). Forensic and statistical data were obtained through data analysis, which revealed a large genetic diversity, with an average value of 0.813 for the analyzed population. The present study was more robust than previous STR marker studies and will contribute to future research on population genetics in Brazil and worldwide. The results of this study allowed the establishment of haplotypes found in the forensic samples of Bahia State to serve as a reference in the elucidation of criminal cases and paternity tests, as well as population and evolutionary investigations.

HLA alleles and antiseizure medication-induced cutaneous reactions in Brazil: A case-control study.

In this observational case-control study, 107 cutaneous adverse reaction (CAR) cases (CAR+) manifesting up to 12 weeks after the start of treatment with antiseizure medication (ASM) were identified. Control groups consisted of 98 epilepsy patients without a history of CAR (CAR-) and 3965 healthy individuals in the Brazilian National Registry of Bone Marrow Donors. All participants were HLA typed by high-resolution Next Generation Sequencing for HLA-A, B, C, DQB1 and DRB1; HLA-DPA1, DPB1, DQA1, DRB3, DRB4 and DRB5 were also sequenced in samples from CAR+ and CAR- individuals. The relationship between the carrier frequency of each allele, CAR type and ASM for all participants was investigated. The ASMs most frequently associated with CAR were carbamazepine (48% of CAR+ subjects), lamotrigine (23%), phenytoin (18%), phenobarbital (13%) and oxcarbazepine (5%). The main alleles associated with a risk of CAR were HLA-A*02:05 (OR = 6.28; p = 0.019, carbamazepine or oxcarbazepine); HLA-DPA1*02:02 (OR = 4.16, p = 0.003, carbamazepine); HLA-B*53:01 (OR = 47.9, p = 0.014, oxcarbazepine), HLA-DPA1*03:01/DPB1*105:01 (OR = 25.7, p = 0.005, phenobarbital); HLA-C*02:10 (OR = 25.7, p = 0.005, phenobarbital) and HLA-DRB1*04:02 (OR = 17.22, p = 0.007, phenytoin). HLA-A*03:01 increased the risk for phenytoin-induced maculopapular exanthema 4.71-fold (p = 0.009), and HLA-B*35:02 was associated with a 25.6-fold increase in the risk of carbamazepine-induced Stevens-Johnson syndrome (p = 0.005). None of the 4170 subjects carried the HLA-B*15:02 allele, and HLA-A*31:01 was not associated with CAR. Hence, HLA-A*31:01 and HLA-B*15:02 were not associated with CAR in this population. Although other HLA class I and II alleles tested were associated with a risk of CAR, none of these associations were strong enough to warrant HLA testing before prescribing ASM.

BRCA1 and BRCA2 germline mutation analysis from a cohort of 1267 patients at high risk for breast cancer in Brazil.

We determined the frequency and mutational spectrum of BRCA1 and BRCA2 in a series of patients at high risk for developing breast cancer from Brazil. A total of 1267 patients were referred for BRCA genetic testing, and no obligation of fulfilling criteria of mutation probability methods for molecular screening was applied. Germline deleterious mutations in BRCA1/2 (i.e., pathogenic/likely pathogenic variants) were identified in 156 out of 1267 patients (12%). We confirm recurrent mutations in BRCA1/2, but we also report three novel mutations in BRCA2, not previously reported in any public databases or other studies. Variants of unknown significance (VUS) represent only 2% in this dataset and most of them were detected in BRCA2. The overall mutation prevalence in BRCA1/2 was higher in patients diagnosed with cancer at age > 35 years old, and with family history of cancer. The present data expand our knowledge of BRCA1/2 germline mutational spectrum, and it is a valuable clinical resource for genetic counseling and cancer management programs in the country.

Ancestry resolution of South Brazilians by forensic 165 ancestry-informative SNPs panel.

Forensic DNA phenotyping (FDP) includes biogeographic ancestry (BGA) inference and externally visible characteristics (EVCs) prediction directly from an evidential DNA sample as alternatives to provide valuable intelligence when conventional DNA profiling fails to achieve identification. In this context, the application of Massively Parallel Sequencing (MPS) methodologies, which enables simultaneous typing of multiple samples and hundreds of forensic markers, has been gradually implemented in forensic genetic casework. The Precision ID Ancestry Panel (Thermo Fisher Scientific, Waltham, USA) is a forensic multiplex assay consisting of 165 autosomal SNPs designed to provide biogeographic ancestry information. In this work, a sample of 250 individuals from Rio Grande do Sul (RS) State, southern Brazil, apportioned into four main population groups (African-, European-, Amerindian-, and Admixed-derived Gauchos), was evaluated with this panel, to assess the feasibility of this approach in a highly heterogeneous population. Forensic descriptive parameters estimated for each population group revealed that this panel has enough polymorphic and informative SNPs to be used as a supplementary instrument in forensic individual identification and kinship testing regardless of ethnicity. No statistically significant deviation from Hardy-Weinberg equilibrium was observed after Bonferroni correction. However, seven loci pairs displayed linkage disequilibrium in pairwise LD testing (p < 3.70 × 10-6). Interpopulation comparisons by FST analysis, MDS plot, and STRUCTURE analysis among the four RS population groups apart and along with 89 reference worldwide populations demonstrated that Admixed- and African-derived Gauchos present the highest levels of admixture and population stratification, whereas European- and Amerindian-derived exhibit a more homogeneous genetic conformation.

Challenges in periodic revision of genetic testing results: Comparison of the main classification guidelines and report of a retrospective analysis involving BRCA1/BRCA2 variants of uncertain significance.

In the context of cancer predisposition syndromes, it is widely known that the correct interpretation of germline variants identified in multigene panel testing is essential for adequate genetic counseling and clinical decision making, in which variants of uncertain significance (VUS) are not considered actionable findings. Thus, their periodic re-evaluation using appropriate guidelines is notably important. In the present study, we compared the performance of the main variant classification guidelines (ACMG, Sherloc and ENIGMA) in variant reassessment, using as input a BRCA1/2 VUS case series (retrospective analysis) from Brazil, an ethnically diverse and admixed country with substantial challenges in VUS reclassification. As main findings, two of the 15 VUS analyzed were reclassified as likely pathogenic by the 3 guidelines, BRCA1 c.4987-3C > G (rs397509213) and BRCA2 c.7868A > G (rs80359012). Moreover, challenges in variant classification and reassessment are described and additional in silico data about structural impact of the variant BRCA2 c.7868A > G are provided. We hypothesize that the establishment of a framework to reassess VUS could improve this process in health centers that have not yet implemented this practice. Results of this study underscore that periodic monitoring of the functional, clinical, and bioinformatics data of a VUS by a multidisciplinary team are of utmost importance in clinical practice. When there is a specific guideline for a given gene, such as ENIGMA for BRCA1/2, it should be considered the first option for variant assessment. Finally, recruitment of VUS carriers and their relatives to participate in variant segregation studies and publication of VUS reclassification results in the international scientific literature should be encouraged.

Estimated polyphenol intake and major food sources of the Brazilian population: changes between 2008-2009 and 2017-2018.

Assessing the dietary intake of polyphenols and their major food sources is the first step towards documenting the associations with health outcomes. Considering recent changes in dietary patterns of the Brazilian population, continuous monitoring of polyphenol intake is important. Thus, the present study was conducted to estimate the polyphenol intake and major food sources in the diet of the Brazilian population using data from the most recent National Dietary Survey (NDS, 2017-2018), to characterise the intake changes according to demographic characteristics and to compare the intake over the past decade in Brazil. Data from two cross-sectional population-based surveys were analyzed in the study. Trends in polyphenol intake and major food sources were estimated using food consumption data from NDS 2008-2009 (n 34 003) and 2017-2018 (n 46 164). The median (25-75th percentiles) of energy-adjusted polyphenol intake in 2017-2018 was 216·3 mg (125·3-495·2 mg) per 1000 kcal/d (4184 kJ/d), representing an increase of 12·3 mg/d from 2008-2009. However, unadjusted polyphenol intakes were similar between the surveys (medians: 364·3 mg/d in 2008-2009 and 366·9 mg/d in 2017-2018). The main food sources of total and polyphenol intake classes presented some variations between 2008-2009 and 2017-2018, with greater contribution of beans preparations, salads and tea to polyphenol intake, and decrease of orange contribution. Our study provided an updated information on polyphenol intake and its major food sources. The median intake remains lower than the reported by other populations. Furthermore, the results may contribute to future studies investigating temporal trends in polyphenol intake and disease risk.

Pharmacogenetic predictors of variability in efavirenz pharmacokinetics in an admixed Brazilian HIV cohort.

AIMS: To investigate the influence of pharmacogenetic polymorphisms on efavirenz (EFV) exposure and metabolism in HIV-infected Brazilians under treatment with EFV-containing antiretroviral (ART) regimens. METHODS: HIV-positive adults (n = 82) on stable ART regimens containing 600 mg EFV once daily for at least 6 months were recruited at 2 university hospitals. Blood samples collected at mid-dose interval were used to quantify the plasma concentrations of EFV (denoted [EFV]), its major metabolite 8-OH-EFV ([8-OH-EFV]) and [8-OH-EFV]/[EFV] metabolic ratio, and to genotype single nucleotide polymorphisms in CYP2B6 (rs3745274, c.516G > T; rs28399499, c.983 T > C) and ABCB1 (rs3842, c.4036G > A). CYP2B6 metabolic phenotypes were inferred from the CYP2B6 diplotypes. Linear regression modelling was applied to identify sociodemographic, clinical and pharmacogenetic predictors of [EFV] and [8-OH-EFV]/[EFV] metabolic ratio. RESULTS: Wide (50-fold) interindividual variation in [EFV], [8-OH-EFV] and [8-OH-EFV]/[EFV] was observed; 69.5% of participants had [EFV] within the nominal therapeutic range (1000-4000 ng/mL), while 19.5 and 11.0% had [EFV] below and above this range, respectively. Multiple regression modelling retained only CYP2B6 metabolic phenotypes or the combined rs3745274 and rs28399499 genotypes, as significant predictors of [EFV] and [8-OH-EFV]/[EFV]. CONCLUSION: EFV exposure and disposition varied widely among HIV-infected Brazilians under stable treatment with EFV-containing ART regimens. About 1/10 of the participants had [EFV] exceeding nominal supratherapeutic concentration (4000 ng/mL), but reported tolerance to the ARV regimens, while 1/5 of participants had nominal subtherapeutic [EFV] (<1000 ng/mL) but adequate virological response. Genotype for the 2 CYP2B6 single nucleotide polymorphisms studied explained 48% of variation in [EFV] and 35% of variation in [8-OH-EFV]/[EFV].

Outcome of sex determination from ulnar and radial ridge densities of Brazilians' fingerprints: Applying an existing method to a new population.

Fingerprints do not repeat, varying from region to region on the same fingerprint and from person to person. Using this morphological exclusivity in the individualization of people is considered one of the most reliable methods of identification worldwide. Many populations have been studied with respect to sex determination from fingerprints. In this study, the ridge density from two different areas - ulnar and radial - of the ten fingerprints from 100 Brazilian men and 100 Brazilian women was ascertained and statistically analyzed. The aim was to check whether these characteristics depended on sex to distinguish them categorically. Women had significantly higher ridge density in both areas for the fingers analyzed globally. Sometimes, men and women showed statistically significant differences in hands and fingers. From ulnar and radial ridge densities, this research developed thresholds for sexual discrimination cases of human identification in Brazil.

Characterization of DNA Polymerase Genes in Amazonian Amerindian Populations.

Due to their continuing geographic isolation, the Amerindian populations of the Brazilian Amazon present a different genetic profile when compared to other continental populations. Few studies have investigated genetic variants present in these populations, especially in the context of next-generation sequencing. Knowledge of the molecular profile of a population is one of the bases for inferences about human evolutionary history, in addition, it has the ability to assist in the validation of molecular biomarkers of susceptibility to complex and rare diseases, and in the improvement of specific precision medicine protocols applied to these populations and to populations with high Amerindian ancestry, such as Brazilians. DNA polymerases play essential roles in DNA replication, repair, recombination, or damage repair, and their influence on various clinical phenotypes has been demonstrated in the specialized literature. Thus, the aim of this study is to characterize the molecular profile of POLA1, POLE, POLG, POLQ, and REV3L genes in Amerindian populations from the Brazilian Amazon, comparing these findings with genomic data from five continental populations described in the gnomAD database, and with data from the Brazilian population described in ABraOM. We performed the whole exome sequencing (WES) of 63 Indigenous individuals. Our study described for the first time the allele frequency of 45 variants already described in the other continental populations, but never before described in the investigated Amerindian populations. Our results also describe eight unique variants of the investigated Amerindians populations, with predictions of moderate, modifier and high clinical impact. Our findings demonstrate the unique genetic profile of the Indigenous population of the Brazilian Amazon, reinforcing the need for further studies on these populations, and may contribute to the creation of public policies that optimize not only the quality of life of this population, but also of the Brazilian population.

Five novel HLA-A, -B, and -C alleles identified in Brazilian individuals by next-generation sequencing.

The novel HLA-A*11:379, B*45:01:11, B*15:571, B*57:137, C*07:893 alleles were identified in Brazilian individuals.

Novel HLA-A, HLA-B, and HLA-DRB1 alleles identified in Brazilian individuals.

Identification of 12 novel HLA class I and II alleles in Brazilian bone marrow donors.