Polymorphisms and gene expression of metalloproteinases and their inhibitors associated with cerebral ischemic stroke in young patients with sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is a genetic disease with great clinical heterogeneity and few viable strategies for treatment; hydroxyurea (HU) is the only widely used drug. Thus, the study of single nucleotide polymorphisms (SNPs) and the gene expression of MMPs 1, 2, 9, 7 and TIMPs 1 and 2, which are involved in the regulation of extracellular matrix, inflammation, and neuropathies, may provide further insights into the pathophysiology of the disease and elucidate biomarkers and molecules as potential therapeutic targets for patients with SCA. METHODS AND RESULTS: We evaluated 251 young individuals with SCA from northeastern Brazil. The groups were divided according to vaso-occlusive crisis (VOC) and cerebrovascular disease (CVD), compared to control individuals. SNP detection and gene expression assays were performed by real-time PCR, TaqMan system®. Both the expression levels of MMP1 gene, and the SNP MMP1-1607 1G/2G were associated with the risk of cerebral ischemic stroke (IS), and the expression of MMP1 was also associated with a higher frequency of VOC/year. Expression levels of MMP7, TIMP1, and TIMP2 were increased in patients conditioned to IS. The SNP 372T>C (rs4898) TIMP1 T alleles were more frequent in patients with > 5 VOC events/year. The SNP rs17576 of MMP9 showed differences in gene expression levels; it was increased in the genotypes AG, and AG+GG. CONCLUSION: The findings of this study, the SNPs, and expression provide initial support for understanding the role of MMPs-TIMPs in the pathophysiology of SCA in young patients.

Aspects of cognitive assessments and spectroscopic magnetic resonance imaging in people with chronic hepatitis C: a systematic review.

Extrahepatic manifestations are common in people with hepatitis C virus (HCV). Cognitive changes are pointed out, but the mechanisms are still uncertain. The aim of this systematic review was to analyze studies involving spectroscopic magnetic resonance in people infected with HCV, which also included cognitive tests. The research occurred in six databases (Directory of Open Access Journals, Lilacs, Medcaribe, Medline, Scielo and ScienceDirect) and the selection of studies was carried out in two stages: search for titles and abstracts, then reading of the full articles, excluding those that did not meet the eligibility criteria. 12,888 titles and abstracts were selected, but only 6 articles were included in the review. Impairments in attention, concentration, speed of information processing, memory, verbal fluency and executive functions were identified as well as an increase in the Cho/Cr and mI/Cr ratios and a reduction in the NAA/Cr ratio in some included studies. Longitudinal studies, with more homogeneous samples and methods, as well as with better controlled confounding factors, are necessary to adequately identify the effect of HCV on the brain.

Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages.

AIMS: Liver fibrosis is the result of an exacerbated wound-healing response associated with chronic liver injury. Interleukin-22 (IL-22) plays a key role in liver disease, through either a protective or an adverse role, depending on the context. The relationship between IL-22 and its receptors IL-22R1 and IL-22BP (soluble inhibitor) in liver fibrosis is unknown. In this study, we assessed the presence and quantity of IL-22, IL-22R1, and IL-22BP-producing cells in liver tissues of patients with chronic hepatitis C. METHODS AND RESULTS: The number of IL-22-producing cells was significantly higher in stages F1, F2, and F3 when compared to F0 or F4 (p < 0.05). The immunostaining of IL-22R1 decreased as liver fibrosis increased from F1 to F4. On the other hand, the concentration of IL-22BP-producing cells was higher in patients with cirrhosis (F4). Furthermore, the IL-22BP:IL-22 ratio was highest in patients with cirrhosis. CONCLUSIONS: Our results suggest that IL-22, IL-22R1 and IL-22BP may be involved in the mechanisms of liver fibrosis in patients with chronic hepatitis C.

Potential role of microRNAs as biomarkers in human glioblastoma: a mini systematic review from 2015 to 2020.

Glioblastoma (GBM) is the most common, aggressive and malignant type of glioma, with poor prognosis, despite advances in medical knowledge and technology. It's known that some microRNAs (miRNAs) can be dysregulated and associated with tumors. We aim to investigate miRNAs that may have a role as potential biomarkers in human glioblastoma. A search was performed using PubMed, LILACS and SCIELO databases to find papers from 2015 to 2020, related to human in vitro and ex vivo data. From 99 articles, 10 were eligible and 13 dysregulated miRNAs were found with description of regulation, target(s), pathway(s) and mechanism(s). The miRNAs of interest were found and seem to be involved in development and progression of glioblastoma and used as target therapies. Understanding the mechanisms in which those miRNAs are involved and their role in epigenetic pathways that lead to cancer, as well as their potential in clinical application, may improve GBM clinical outcome (CRD42020182706, 07/10/2020, retrospectively registered).

Higher levels of TNF and IL-4 cytokines and low miR-182 expression in visceral leishmaniasis-HIV co-infected patients.

AIMS: The aim of the present study was to assess serum cytokine and miRNA expression in visceral leishmaniasis-HIV (VL-HIV) co-infection and HIV mono-infection. METHODS AND RESULTS: We analysed 113 serum samples from HIV patients in areas endemic for leishmaniasis. The diagnosis of VL was confirmed in 65 of these 113 samples. The VL-HIV and HIV groups presented significant differences regarding haemoglobin level (P < .0001), lymphocyte count (P = .0444), white blood cell count (P = .0108), weight loss (P = .0310), HIV load (P < .0001) and CD4+ T-lymphocytes count (P = .0003). Levels of IL-6 and IL-10, IFN-γ and IL-6, IFN-γ and IL-10, TNF and IL-2 were positively correlated in VL-HIV co-infection, indicating higher serum levels of TNF and IL-4 (P < .0001). In addition, miR-182 expression was found to be significantly higher in HIV (P = .009), miR-210 exhibited no statistically significant difference between groups, and nonexpression of miR-122 was found in both groups. CONCLUSION: Together, TNF, IL-4 and miR-182 may represent circulatory biomarkers of VL-HIV co-infection.

SLC11A1 (rs3731865) polymorphism and susceptibility to visceral leishmaniasis in HIV-coinfected patients from Northeastern Brazil.

Following the emergence of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis-HIV (VL-HIV) coinfections has increased worldwide, mainly in Brazil. The development of clinical forms of VL can be influenced by nutritional status, age, and host genetic factors, which are important variables determining susceptibility to disease. There are no studies with a candidate gene approach assayed directly in the VL-HIV-coinfected population. Herein, we determined and analyzed the associations of SLC11A1, LECT2, CCL1, CCL16, and IL4 genetic polymorphisms with susceptibility to VL-HIV coinfection in Northeastern Brazil. We analyzed 309 DNA samples extracted from the peripheral blood of HIV patients, and clinical and hematological data were collected from medical records. The diagnosis of VL was confirmed in 110 out of 309 patients; genotyping was carried out by TaqMan assays afterwards. Our results confirmed the association between the SLC11A1 polymorphism (rs3731865) and VL-HIV coinfection (p = 0.0206, OR 1.8126, 95% CI 1.1050-2.9727). In addition, the SLC11A1 genotype GG (p = 0.0050, OR 3.0395, 95% CI 1.4065-6.5789) and CD4+ T lymphocyte count (p = 0.0030, OR 0.9980, 95% CI 0.9970-0.9990) were associated with VL-HIV coinfection in a multivariate model. The polymorphism of the SLC11A1 gene (rs3731865) was associated with VL-HIV coinfection, suggesting a possible genetic mechanism involved in the susceptibility to VL in HIV patients. This finding can suggest new therapeutic targets and genetic markers for the VL-HIV-coinfected population.

Combined genotypes of the MBL2 gene related to low mannose-binding lectin levels are associated with vaso-occlusive events in children with sickle cell anemia.

Sickle cell anemia (SCA) presents heterogenous clinical manifestations that cannot be explained solely by alterations to hemoglobin (Hb); other components such as endothelial adhesion, thrombosis and inflammation may be involved. The mannose-binding lectin (MBL) has an important role in innate immunity and inflammatory diseases. In this report, we describe an association between MBL2 polymorphism related to low production of serum MBL and the frequency of vasoocclusive events (FVOE) in children ≤ 5 years old with SCA (p = 0.0229; OR 5.55; CI 1.11-27.66). Further studies are needed to explore the role of low MBL2 in the pathophysiology of vasoocclusive events in SCA.

TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals.

Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti-inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF-α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-α -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. © 2016 Wiley Periodicals, Inc.

Predicting the outcome of death by CALL Score in COVID-19 patients.

OBJECTIVE: The aim of this study was to assess the performance of the CALL Score tool in predicting the death outcome in COVID-19 patients. METHODS: A total of 897 patients were analyzed. Univariate and multivariate logistic regression analyses were conducted to determine the association between characteristics of the CALL Score and the occurrence of death. The relationship between CALL Score risk classification and the occurrence of death was also examined. Receiver operating characteristic curve analysis was performed to identify optimal cutoff points for the CALL Score and the outcome. RESULTS: The study revealed that age>60 years, DHL>500, and lymphocyte count ≤1000 emerged as independent predictors of death. Higher risk classifications of the CALL Score were associated with an increased likelihood of death. The optimal CALL Score cutoff point for predicting the death outcome was 9.5 (≥9.5), with a sensitivity of 70.4%, specificity of 80.3%, and accuracy of 80%. CONCLUSION: The CALL Score showed promising discriminatory ability for death outcomes in COVID-19 patients. Age, DHL level, and lymphocyte count were identified as independent predictors. Further validation and external evaluation are necessary to establish the robustness and generalizability of the CALL Score in diverse clinical settings.

High production MBL2 polymorphisms protect against COVID-19 complications in critically ill patients: A retrospective cohort study.

Mannose-binding lectin (MBL) binds to SARS-CoV-2, inhibits infection of susceptible cells, and activates the complement system via the lectin pathway. In this study, we investigated the association of MBL2 polymorphisms with the risk of hospitalization and clinical worsening in patients with COVID-19. A total of 550 patients with COVID-19 were included (94 non-hospitalized and 456 hospitalized). Polymorphisms in MBL2 exon 1 (codons 52, 54 and 57) and promoter region (-550, -221, and +4) were determined by real-time PCR. MBL and complement proteins were measured by Luminex. A higher frequency of the H/H genotype and the HYPA haplotype was observed in non-hospitalized patients when compared to hospitalized. In addition, critically ill patients carrying haplotypes associated with high MBL levels (HYPA/HYPA + HYPA/LYPA + HYPA/LYQA + LYPA/LYQA + LYPA/LYPA + LYQA/LYQA + LXPA/HYPA + LXPA/LYQA + LXPA/LYPA) were protected against lower oxygen saturation levels (P = 0.02), use of invasive ventilation use (P = 0.02, OR 0.38), and shock (P = 0.01, OR 0.40), independent of other potential confounders adjusted by multivariate analysis. Our results suggest that variants in MBL2 associated with high MBL levels may play a protective role in the clinical course of COVID-19.

Dynamics of the Trypanosoma cruzi infection in adipose tissue: Assessing gene expression of PNPLA2, FASN, and ACAT1 under Benzonidazole treatment and indirect mononuclear immune cells interaction.

Trypanosoma cruzi is a parasite with a high capacity to adapt to the host. Animal models have already demonstrated that the tropism of this parasite occurs not only in cardiac/digestive tissues but also in adipose tissue (AT). That said, the consequences ofT. cruziinfection for AT and the implications of treatment with Benzonidazole in this tissue are under discussion. Here, we tested the hypothesis that T. cruzi infection in adipose tissue upon treatment with Benzonidazole (Bz) and the interaction of mononuclear immune cells (PBMC) influences the relative expression of ACAT1, FASN, and PNPLA2 genes. Thus, stem cells derived from adipose tissue (ADSC) after adipogenic differentiation were indirectly cultivated with PBMC after infection with the T. cruzi Y strain and treatment with Bz. We use the TcSAT-IAM system and RT-qPCR to evaluate the parasite load and the relative quantification (ΔCt) of the ACAT1, FASN, and PNPLA2 genes. Our results demonstrate that treatment with Bz did not reduce adipocyte infection in the presence (p-value: 0.5796) or absence (p-value: 0.1854) of cultivation with PBMC. In addition, even though there is no statistical difference when compared to the control group (AT), T. cruzi induces the FASN expression (Rq: 14.00). However, treatment with Bz in AT suggests the increases of PNPLA2 expression levels (Rq: 12.58), even in the absence of T. cruzi infection. During indirect cultivation with PBMC, T. cruzi smooths the expression of PNPLA2 (Rq: 0.824) and instigates the expression of ACAT1 (Rq: 1.632) and FASN (Rq: 1.394). Furthermore, the treatment with Bz during infection induces PNPLA2 expression (Rq: 1.871), maintaining FASN expression levels (Rq: 1.334). Given this, our results indicate that treatment with Benzonidazole did not decrease T. cruzi infection in adipose tissue. However, treating the adipocyte cells with Bz during the interaction with PBMC cells influences the lipid pathways scenario, inducing lipolytic metabolism through the expression of PNPLA2.

Human Genome Polymorphisms and Computational Intelligence Approach Revealed a Complex Genomic Signature for COVID-19 Severity in Brazilian Patients.

We present a genome polymorphisms/machine learning approach for severe COVID-19 prognosis. Ninety-six Brazilian severe COVID-19 patients and controls were genotyped for 296 innate immunity loci. Our model used a feature selection algorithm, namely recursive feature elimination coupled with a support vector machine, to find the optimal loci classification subset, followed by a support vector machine with the linear kernel (SVM-LK) to classify patients into the severe COVID-19 group. The best features that were selected by the SVM-RFE method included 12 SNPs in 12 genes: PD-L1, PD-L2, IL10RA, JAK2, STAT1, IFIT1, IFIH1, DC-SIGNR, IFNB1, IRAK4, IRF1, and IL10. During the COVID-19 prognosis step by SVM-LK, the metrics were: 85% accuracy, 80% sensitivity, and 90% specificity. In comparison, univariate analysis under the 12 selected SNPs showed some highlights for individual variant alleles that represented risk (PD-L1 and IFIT1) or protection (JAK2 and IFIH1). Variant genotypes carrying risk effects were represented by PD-L2 and IFIT1 genes. The proposed complex classification method can be used to identify individuals who are at a high risk of developing severe COVID-19 outcomes even in uninfected conditions, which is a disruptive concept in COVID-19 prognosis. Our results suggest that the genetic context is an important factor in the development of severe COVID-19.

MicroRNA dysregulation in schistosomiasis-induced hepatic fibrosis: a systematic review.

BACKGROUND: MicroRNAs are involved in gene regulation in several common liver diseases and may play an essential role in activating hepatic stellate cells. The role of these post-transcriptional regulators in schistosomiasis needs to be further studied in populations from endemic areas for a better understanding of the disease, the development of new therapeutic approaches, and the use of biomarkers for the prognosis of schistosomiasis. AREAS COVERED: We performed a systematic review to describe the main human microRNAs identified in non-experimental studies associated with aggravation of the disease in people infected with Schistosoma mansoni (S. mansoni) and Schistosoma japonicum (S. japonicum). Structured searches were carried out in PubMed, Medline, Science Direct, Directory of Open Access Journals, Scielo, Medcarib, and Global Index Medicus databases without time and language restrictions. This is a systematic review following the guidelines of the PRISMA platform. EXPERT OPINION: The miR-146a-5p, miR-150-5p, let-7a-5p, let-7d-5p, miR-92a- 3p, and miR-532-5p are associated with liver fibrosis in schistosomiasis caused by S. japonicum, revealing that these miRNAs that have been shown to be associated with liver fibrosis are good targets for new studies that evaluate their potential as a biomarker or even treating liver fibrosis in schistosomiasis.

A Polymorphism in the TMPRSS2 Gene Increases the Risk of Death in Older Patients Hospitalized with COVID-19.

BACKGROUND: Transmembrane serine protease type 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) are the main molecules involved in the entry of SARS-CoV-2 into host cells. Changes in TMPRSS2 expression levels caused by single nucleotide polymorphisms (SNPs) may contribute to the outcome of COVID-19. The aim was to investigate the association between TMPRSS2 gene polymorphisms and the risk of death in hospitalized patients with COVID-19. METHODS: We included patients with confirmed COVID-19, recruited from two hospitals in northeastern Brazil from August 2020 to July 2021. Two functional polymorphisms (rs2070788 and rs12329760) in TMPRSS2 were evaluated by real-time PCR. The Kaplan-Meier method was used to estimate death. The Cox's proportional hazards model was used to adjust for potentially confounding factors. RESULTS: A total of 402 patients were followed prospectively. Survival analysis demonstrated that older patients carrying the rs2070788 GG genotype had shorter survival times when compared to those with AG or AA genotypes (p = 0.009). In multivariable analysis, the GG genotype was a factor independently associated with the risk of death in older individuals (hazard ratio = 4.03, 95% confidence interval 1.49 to 10.84). CONCLUSIONS: The rs2070788 polymorphism in TMPRSS2 increases risk of death four-fold in older patients hospitalized with COVID-19.

Lack of Association of Polymorphisms in IL22 and IL22RA1 Genes with Fibrosis Severity in Patients with Chronic Hepatitis C.

The IL-22 pathway has been shown to play an important role in the pathogenesis of liver fibrosis. However, little is known about the role of single-nucleotide polymorphisms (SNPs) in IL-22-related genes in relation to the severity of liver fibrosis. This study aimed to investigate the association of polymorphisms in IL22 and IL22RA1 genes with the severity of liver fibrosis in patients with chronic hepatitis C. A total of 326 patients (165 with mild fibrosis and 161 with severe fibrosis) were included. Four SNPs in IL22 (rs1179251, rs2227473, rs1012356, and rs2227485) and two in IL22RA1 (rs4648936 and rs3795299) were evaluated by real-time PCR. No significant association was observed between the polymorphisms studied and the severity of liver fibrosis. The SNPs rs1179251, rs2227473, rs1012356, and rs2227485 in IL22 and rs4648936 and rs3795299 in IL22RA1 may not be involved in the pathogenesis of liver fibrosis in patients with chronic hepatitis C.

Mannose-binding lectin levels and MBL2 gene polymorphisms are associated with dengue infection in Brazilian children at the early ages.

BACKGROUND: The mannose-binding lectin (MBL) plays an important role in innate immunity. Genetically determined variations in serum levels of MBL may influence the susceptibility and clinical outcome of dengue infection in early life. METHODS: We investigated the MBL2 gene polymorphisms and serum levels of MBL (total and functional) in children with asymptomatic (n=17) and symptomatic (n=29) primary dengue infections and age-matched uninfected children (n=84) enrolled in a birth cohort with dengue in Brazil. Polymorphisms of the MBL2 gene were assessed by reverse transcription-polymerase chain reaction (RT-PCR), whereas the enzyme-linked immunosorbent assay (ELISA) was used to quantify serum levels of MBL. RESULTS: We found that the X allele and YX genotype in the MBL2 were more frequent in the dengue cases than in the control group. Likewise, the LXPA haplotype was exclusively found in dengue cases, thus probably related to dengue infection in our setting. Moreover, we found a higher frequency of the O allele and AO genotype in the control group. Serum levels of total and functional MBL were higher in dengue naïve infants than in dengue cases. CONCLUSIONS: MBL2 variants related to lower production of serum MBL were associated with dengue infection in infants, whereas intermediate to high levels of total and functional serum MBL were associated with protection against dengue infection. These findings highlight the role of MBL2 variants and serum levels of MBL in the susceptibility of children to dengue disease at early ages.

The role of Mannose-binding lectin in leprosy: A systematic review.

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an acute phase protein associated with the pathophysiology of leprosy. Some studies have shown that there is a correlation between serum levels of MBL and polymorphisms in its gene associated with susceptibility per se and to different clinical forms. The aim of this study was to conduct a systematic review of publications in the literature that studied the association of MBL with leprosy. Databases were searched until December 2020 (PROSPERO: CRD42020158458), and additional searches were conducted scanning the reference lists of the articles. Two independent reviewers assessed the study quality using the Newcastle-Ottawa Quality Assessment Scale. Finally, 10 eligible articles were included in the study. The overall results indicated that both low MBL serum levels and polymorphisms in the structural or promoter region of its gene seem to be associated as protective factors against the development of severe forms. The results suggest that MBL may play a role in the clinical progression of leprosy.

Clinical and laboratory parameters associated with li-rads as diagnostic of liver nodule in patients with cirrhosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Clinical and laboratory evaluation of a cirrhotic patient with a liver nodule may show alterations suggesting malignancy. There is a lack of questions related to diagnosis of HCC and evaluation of liver imaging reporting and data system (LI-RADS) could be a tool for early diagnosis of HCC. This aims to confirm an association between clinical and laboratory characteristics in cirrhotic patients with hepatic nodule after LI-RADS categorization. METHODS: A cross-sectional retrospective study was performed with 62 patients grouped according to LI-RADS algorithm. Differences between groups were confirmed using association tests and the Kappa test was employed to provide further confirmation. RESULTS: Associations were observed after univariate analysis with higher values of aspartate aminotransferase (AST) (P=0.008), alanine aminotransferase (ALT) (P=0.019), alkaline phosphatase (ALP) (P=0.0052), gamma glutamyl transferase (GGT) (P=0.0023), alpha-fetoprotein (AFP) (P=0.0001), nodule size (P=0.0001) and age (P=0.007) in LR 5 group compared to LR 3. Univariate analysis also revealed higher levels for the LR5 group of ALP (P=0.0228), AFP (P=0.022) and age (P=0.046) in relation to LR 1+2 group. AFP also had higher serum levels in the LR 4 group compared to LR 1+2 (P=0.004). After multivariate analysis, higher levels in LR5 group of nodule size (P=0.047) and ALP (P=0.027) were observed in relation to LR3, and were therefore considered predictors of HCC diagnosis. CONCLUSIONS: The study suggests that the combination of clinical-laboratory and radiological factors, such as heightened serum levels of ALP and hepatic nodule size, may support the screening of HCC in cirrhotic patients with hepatic nodules using the LI-RADS algorithm.

The 1G/1G+1G/2G Genotypes of MMP1 rs1799750 Are Associated with Higher Levels of MMP-1 and Are Both Associated with Lipodystrophy in People Living with HIV on Antiretroviral Therapy.

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the MMP1 gene (rs1799750) (1G/2G) and the serum levels of matrix metalloproteinase 1 (MMP-1) with LD and its subtypes in people living with HIV on ART. This is a cross-secional study. LD was self-reported. The determination of the MMP1 rs1799750 gene polymorphism was performed by real-time PCR, and the serum concentrations of MMP-1 were quantified by the enzyme-linked immunosorbent assay (ELISA) method. Of 404 participants, 204 (51%) were diagnosed with LD, of whom 89 (43%) had mixed lipodystrophy (ML), 72 (35%) had lipohypertrophy (LH), and 43 (22%) had lipoatrophy (LA). There was an association between the genotypes 1G/1G+1G/2G and higher serum levels of MMP-1 (p = .025). There was no association of MMP1 (1G/2G) with LD. Other factors associated with LD were current CD4 ≤ 350 [odds ratio (OR) = 4.85, confidence interval (CI) = 1.78-47.99, p = .0033] and serum MMP-1 levels >6.81 (OR = 2.67, CI = 1.21-6.08, p = .0165). Factors associated with ML: current CD4 ≤ 350 (OR = 5.59, CI = 1.69-20.39, p = .006); with LH: number of antiretroviral regimens used: 2 (OR = 2.06, CI = 1.01-4.20, p = .0460) and 3+ (OR = 2.09, CI = 1.00-4.35, p = .0477), and current CD4 ≤ 350 (OR = 2.08, CI = 1.00-4.24, p = .0461); and with LA: current viral load >40 (OR = 2.52, CI = 1.03-5.91, p = .0372) and current use of zidovudine (OR = 2.97, CI = 1.32-6.54, p = .0074). Higher levels of MMP-1 were associated with genotypes 1G/2G+1G/1G and with LD. Other individual risk factors were independently associated with LD, and its subtypes, suggesting that the pathogenesis itself is differently manifested for each type of LD.

Expression of microRNAs (133b and 138) and Correlation with Echocardiographic Parameters in Patients with Alcoholic Cardiomyopathy.

INTRODUCTION: Alcoholic Cardiomyopathy (ACM) is a disease with a difficult diagnosis. The real mechanisms related to its pathophysiology are not fully understood. OBJECTIVE: The aims of this study were to investigate whether miR-133b and miR-138 could be associated with ACM. METHODS: Forty-four patients were included comprising 24 with ACM and 20 with cardiomyopathies of different etiologies (control group). Real-time PCR was performed to verify the relative expression among the studied groups. In the statistical analysis, the quantitative variables t-student Mann- Whitney and correlation of Pearson tests were carried out, while the qualitative variable comprised the chi-square test, with p<0.05 being considered statistically significant. RESULTS: There was no association between clinical and sociodemographic characteristics of the groups. The patients with ACM presented downregulation of miR-133b in comparison with control patients (p=0.004). On the other hand, for the miR-138, there was no association when the ACM group was compared with the control group. The presence of miR-133b among cases and controls was not correlated with any of the echocardiographic parameters. However, the increase in the expression of miR-138 was correlated with an increase in the ejection fraction (r=0.28, p=0.01) and the diameter of the left atrium (r=0.23, p=0.04) in patients with ACM. CONCLUSION: The downregulation of miR-133b might be a marker for ACM and, in addition, miR- 138 could be used to correlate the increase in ejection fraction with and normalization of the diameter of the left atrium diameter in patients with this disease.