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Alzheimer's disease (AD) is the most common type and accounts for 60%–70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non‐coding RNAs that play a crucial role in gene expression regulation. Although the diagnosis of AD is primarily clinical, several miRNAs have been associated with AD and considered as potential markers for diagnosis and progression of AD. We sought to match AD‐related miRNAs in cerebrospinal fluid (CSF) found in the GeoDataSets, evaluated by machine learning, with miRNAs listed in a systematic review, and a pathway analysis. Using machine learning approaches, we identified most differentially expressed miRNAs in Gene Expression Omnibus (GEO), which were validated by the systematic review, using the acronym PECO—Population (P): Patients with AD, Exposure (E): expression of miRNAs, Comparison (C): Healthy individuals, and Objective (O): miRNAs differentially expressed in CSF. Additionally, pathway enrichment analysis was performed to identify the main pathways involving at least four miRNAs selected. Four miRNAs were identified for differentiating between patients with and without AD in machine learning combined to systematic review, and followed the pathways analysis: miRNA‐30a‐3p, miRNA‐193a‐5p, miRNA‐143‐3p, miRNA‐145‐5p. The pathways epidermal growth factor, MAPK, TGF‐beta and ATM‐dependent DNA damage response, were regulated by these miRNAs, but only the MAPK pathway presented higher relevance after a randomic pathway analysis. These findings have the potential to assist in the development of diagnostic tests for AD using miRNAs as biomarkers, as well as provide understanding of the relationship between different pathophysiological mechanisms of AD. [ABSTRACT FROM AUTHOR]

Hydroxyurea has long been used for the treatment of sickle cell anemia (SCA), and its clinical effectiveness is related to the induction of fetal hemoglobin (HbF), a major modifier of SCA phenotypes. However, there is substantial variability in response to hydroxyurea among patients with SCA. While some patients show an increase in HbF levels and an ameliorated clinical condition under low doses of hydroxyurea, other patients present a poor effect or even develop toxicity. However, the effects of genetic polymorphisms on increasing HbF levels in response to hydroxyurea in patients with SCA (Hb SS) have been less explored. Therefore, we performed a systematic review to assess whether single-nucleotide polymorphisms (SNPs) affect HbF levels in patients with SCA treated with hydroxyurea. Moreover, we performed pathway analysis using the set of genes with SNPs found to be associated with changes in HbF levels in response to hydroxyurea among the included studies. The systematic literature search was conducted on Medline/PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Web of Science. Seven cohort studies were included following our inclusion and exclusion criteria. From the 728 genetic polymorphisms examined in the included studies, 50 different SNPs of 17 genes were found to be associated with HbF changes in patients with SCA treated with hydroxyurea, which are known to affect baseline HbF but are not restricted to them. Enrichment analysis of this gene set revealed reactome pathways with the lowest adjusted p -values and highest combined scores related to VEGF ligand–receptor interactions (R-HSA-194313; R-HSA-195399) and the urea cycle (R-HSA-70635). Pharmacogenetic studies of response to hydroxyurea therapy in patients with SCA are still scarce and markedly heterogeneous regarding candidate genes and SNPs examined for association with HbF changes and outcomes, suggesting that further studies are needed. The reviewed findings highlighted that similar to baseline HbF, changes in HbF levels upon hydroxyurea therapy are likely to be regulated by multiple loci. There is evidence that SNPs in intron 2 of BCL11A affect HbF changes in response to hydroxyurea therapy, a potential application that might improve the clinical management of SCA. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=208790). [ABSTRACT FROM AUTHOR]

Background: Approximately 55 million people live with dementia, and 10 million cases are diagnosed each year worldwide (1). Alzheimer's disease (AD) is the most common type of dementia and accounts for 60% ‐ 70% of reported cases (1). MicroRNAs are small non‐coding RNAs that present highly conserved sequences, involved in gene modulation and several molecular mechanisms (2). The miRNAs can be found in cerebrospinal fluid (CSF) and they are potential biomarkers for AD diagnosis (3). This study aimed to perform a systematic review about the expression of miRNAs in the CSF of AD patients compared to cognitive controls and carry out an analysis of the biological pathways regulated by these miRNAs Method: A systematic literature search was performed in Medline/PubMed, the Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Web of Science, Embase and gray literature, including observational studies that evaluated patients with AD and healthy individuals, which evaluated the miRNA expression in CSF. To verify the main signaling pathways regulated by the miRNAs, the software Gene Cards was used (table 1). Result: 2060 studies were retrieved and, after removing duplicates and reading titles, abstracts and full text, 26 studies met the inclusion criteria. We identified 171 differentially expressed miRNAs between AD and controls. Among them, the miRNAs ‐125b, ‐125‐5p, ‐138‐5p and ‐485‐5p presented differentiated expression between the groups commonly in these studies. The evaluation of signaling pathways showed that regulation of gene expression, cell proliferation, and gene silencing, are regulated by these miRNAs. Conclusion: Our results suggest that the miRNAs ‐125b, ‐125‐5p, ‐138‐5p and ‐485‐5p are involved in AD‐related biological pathways and are potential CSF biomarkers to AD diagnosis. 1. DEMENTIA. World Health Organization, 2022. Available at: . Access at 21 jan. 2023. 2. CORREIA DE SOUSA, Marta et al. Deciphering miRNAs' action through miRNA editing. International Journal of Molecular Sciences, v. 20, n. 24, p. 6249, 2019. 3. TAKOUSIS, Petros et al. Differential expression of microRNAs in Alzheimer's disease brain, blood, and cerebrospinal fluid. Alzheimer's & Dementia, v. 15, n. 11, p. 1468‐1477, 2019. [ABSTRACT FROM AUTHOR]

Introduction:Variations in blood pressure (BP) are, in part, genetically determined and some polymorphisms of renin-angiotensin- aldosterone system (RAAS) and synthase of endothelial nitric oxide (eNOS) have been related to hypertension (HT). Conversely, physical exercise is considered a non-pharmacological tool for HT control, treatment, and prevention. Objective: The purpose of this study is to investigate the relationship between eNOS and RAAS polymorphisms, their epistatic interaction, and the respective humoral factors in the BP control in normotensive/pre-hypertension and hypertensive older adults and how this relationship can be modulated by training status (TS) level. Methods:A total of 155 older adults (66.94 ± 6.83 years old) performed the following evaluations: AAHPERD battery test to determine the general functional fitness index (GFFI), systolic and diastolic blood pressure (SBP and DBP), blood collection for DNA extraction, analysis of eNOS gene polymorphisms rs2070744; rs61722009 and rs1799983 and RAAS polymorphisms rs699; rs1799752 and rs5186, and quantification of ACE activity (Fluorimetric Assay) and nitrite concentration (Chemiluminescence Method). Results and Conclusion:Good TS level appears to exert greater influence on SBP for G2 and G3 (G1: 125.79 ± 14.03/ G2: 119.91 ± 11.72/G3: 119.71 ± 10.85) and on NO2 for G3 (G1: 0.42 ± 0.25/ G2: 0.54 ± 0.45/ G3: 0.71 ± 0.52). No associations were observed between eNOS and RAAS polymorphisms, but the epistasis was identified between eNOS polymorphism, rs2070744, and RAAS polymorphism, rs699, revealing a statistically significant interaction (p =.0235) with training score of 0.63, a training test accuracy of 0.61 and a cross-validation consistency of 10/10. This result suggests an increased risk of hypertension. [ABSTRACT FROM AUTHOR]

A study was undertaken to assess the reliability and accuracy of Ancestry informative markers (AIMs) in defining admixture estimation among South American indigenous populations. Results showed that AIMs in certain cases might be applicable but consideration should be given for the possibility of genetic drift.

The genomic ancestry of a Brazilian population sample from the State of Sao Paulo is verified, based on autosomal short-tandem repeat (STR) loci. The Unweighted Pair-Group Method with Arithmetic Mean (UPGMA) tree constructed based on genetic distances reveals that the population was grouped with Europeans, and separated from African and Amerindian populations, with 79%European, 14% African and 7% Amerindian admixture component contribution to the sample.

Background: Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods: Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings: European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions: Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil. [ABSTRACT FROM AUTHOR]

Chaudhary and colleagues observed associations of matrix metalloproteinase ( MMP) -2 (-1306C/T) and MMP-9 (-1562C/T) promoter polymorphisms with head and neck squamous cell carcinoma (HNSCC), but not with oral submucous fibrosis (OSMF) in an Indian population. We suggest that they could carry out a haplotype analysis with their data on MMP-2 genotypes (-1306C/T and -168G/T) and that they consider genotyping the microsatellite -90 (CA)14-24 in the MMP-9 promoter region in order to perform haplotype analysis in combination with their data on MMP-9 (-1562C/T) polymorphism. These suggestions could provide additional information with clinical relevance to cancer susceptibility. [ABSTRACT FROM AUTHOR]

Valenzuela and colleagues have recently reviewed some polymorphisms in important candidate genes involved in different pathogenic mechanisms related to preeclampsia (PE) and concluded that various studies in different populations have identified maternal polymorphisms associated with PE. However, we would like to contribute to some studies regarding candidate genes related to angiogenesis and endothelial dysfunction in PE performed in the Brazilian population. Specifically, genotypes and haplotypes formed by polymorphisms of VEGF, eNOS and MMP-9, along with an example of the interaction among these genes in the prediction of PE. Our suggestions may provide additional information with clinical relevance to PE susceptibility. [ABSTRACT FROM AUTHOR]

Lifelong glucocorticoid (GC) replacement is the mainstay treatment of congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD). Challenges posed by therapeutic management of these patients are well known, but novel insights into the variability in clinical response to GC highlight a role for single nucleotide polymorphisms (SNPs) of the glucocorticoid receptor gene (NR3C1). To assess whether six commonly studied NR3C1 SNPs, which were previously associated with modified response to GC, are associated with CAH. We further assessed the linkage disequilibrium (LD) among these NR3C1 SNPs and their combination into haplotypes. Genotypes were determined by Taqman allele discrimination assays for Tth111 I (rs10052957), ER22 (rs6189), 23 EK (rs6190), N363S (rs56149945), BclI (rs41423247) and 9β (rs6198) in a Brazilian cohort of 102 unrelated 21-OHD patients and 163 unrelated healthy subjects (controls). Haplotypes were estimated using Haplo.stats, and LD among SNPs using Haploview. Heterozygous subjects for Tth111 I were more frequent in 21-OHD patients (P = 0.004), while heterozygous for BclI were more frequent in controls (P = 0.049). We found a strong LD among the six NR3C1 SNPs, and four out of six common haplotypes contained the Tth111 I - variant. Although we found no significant differences in overall haplotype analysis, the BclI -haplotype was less frequent among 21-OHD patients (P = 0.0180). BclI -haplotype was less common and heterozygous for Tth111 I were more frequent in 21-OHD patients, while heterozygous for BclI were more frequent in controls. Our novel findings may contribute to further clinical studies on the prognostic value of NR3C1 haplotypes towards individualized treatment for 21-OHD patients. • Glucocorticoid replacement in patients with congenital adrenal hyperplasia is a challenge. • NR3C1 polymorphisms play a role on variable clinical response to glucocorticoids. • Heterozygous- Tht111 I was more frequent in cases with congenital adrenal hyperplasia. • Heterozygous- BclI was more frequent in healthy subjects from the control group. • The BclI -haplotype was less frequent in cases with congenital adrenal hyperplasia. [ABSTRACT FROM AUTHOR]

Objective: To examine whether the DDAH2 promoter polymorphisms -1415G/A (rs2272592), -1151A/C (rs805304) and -449G/C (rs805305), and their haplotypes, are associated with PE compared with normotensive pregnant women, and whether they affect ADMA levels in these groups., Methods: A total of 208 pregnant women were included in the study and classified as early-onset (N=57) or late-onset PE (N =49), and as normotensive pregnant women (N = 102)., Results: Pregnant with early-onset PE carrying the GC and GG genotypes for the DDAH2 -449G/C polymorphism had increased ADMA levels (P=0.01). No association of DDAH2 polymorphisms with PE in single-locus analysis was found. However, the G-C-G haplotype was associated with the risk for late-onset PE., Conclusion: It is suggested that DDAH2 polymorphisms could affect ADMA levels in PE, and that DDAH2 haplotypes may affect the risk for PE., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Objective:  We examined the interaction of polymorphisms in the genes heme oxygenase-1 ( HMOX1 ) and nitric oxide synthase ( NOS3 ) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy., Methods:  The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 ( HO-1) were measured using enzyme-linked immunosorbent assay (ELISA)., Results:  We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA., Conclusion:  We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE., Competing Interests: The authors have no conflicts of interest to to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)