A Relação entre Compartimentos de Volume Extracelular e Matriz Metaloproteinase 2 na Remodelação do Ventrículo Esquerdo após o Infarto do Miocárdio

Background:Matrix metalloproteinases (MMPs) can affect myocardial extracellular volume (ECV) and its compartments, and this can provide more detailed information about the mechanism of adverse left ventricular (LV) remodeling (AR) after acute myocardial infarction (MI).Objectives:To investigate the role of changes (Δ) in ECV compartments (matrix volume (MVi) and cell volume (CVi)) in the development of AR after MI, and their relationship with MMP-2 expressions.Methods:Ninety-two first MI patients who underwent 3 Tesla cardiovascular magnetic resonance imaging performed 2 weeks (baseline) and 6 months post-MI. We measured T1 mapping with MOLLI sequences. ECV was performed post-gadolinium enhancement. ECV and LV mass were used to calculate MVi and CVi. AR was defined as an increase of ≥ 12% in LV end-diastolic volume in 6 months. MMPs were measured using a bead-based multiplex immunoassay system at first day (baseline) and 2 weeks post-MI. P <0.05 was accepted as statistically significant.Results:Mean ECV and mean MVi baseline levels were higher in AR group compared to without AR group (42.9±6.4 vs 39.3±8.2%, p= 0.037; 65.2±13.7 vs 56.7±14.7 mL/m², p=0.010; respectively). CVi levels was similar between groups. A positive correlation was found between baseline levels of MMP-2 and baseline levels of ECV (r=0.535, p<0.001) and MVi (r=0.549, p<0.001). Increased ΔMVi levels was independently predictor of AR (OR=1.03, p=0.010). ΔMVi had superior diagnostic performance compared to ΔECV in predicting AR (ΔAUC: 0.215±0.07, p<0.001).Conclusion:High MVi levels are associated with AR, and ΔMVi was independently predictor of AR. This may be associated with MMP-2 release due to increased inflammatory response.     

Association between factor V Leiden mutation and coronary artery disease in the northeast region of Turkey.

Factor V Leiden (FVL) has recently been described as a genetic factor with a propensity towards venous thromboembolism; however, it is thought to have a doubtful role in coronary artery disease (CAD). This study aimed to investigate whether FVL is one of the risk factors for CAD in north-east Turkey. Seventy-five patients with angiographically documented CAD and 78 individuals without angiographically documented CAD were studied to examine the association of the frequency of the FVL mutation with CAD and control individuals. Blood samples from the patients and controls were analyzed for the FVL mutation by DNA analysis, using the polymerase chain reaction-sequence-specific primers method. FVL mutation was found in eight of 75 (10%) patients with CAD and was totally absent in control individuals (P = 0.001). There were no significant differences in terms of diabetes mellitus, hypertension, dyslipidemia, plasma fibrinogen level, smoking, gender and family history of CAD with and without the FVL mutation in the patient group. The results of this study suggest that FVL mutation may be one of the important risk factors in developing CAD in northeast Turkey.     

Association between alopecia areata and HLA Class I and II in Turkey

HLA class I and II alleles have been described in patients with alopecia areata (AA). As in other immune mediated diseases, the HLA alleles associated with AA may influence the patient's ability to respond to immune challenges from both self and non-self antigens and can offer clues to the cause, prognosis, and potential therapy for the disease. The aim of this study was to determine which HLA class I and II alleles are associated with Turkish alopecia areata patients. Sixty-three patients with AA, alopecia totalis, or alopecia universalis were included in this study and compared with seventy-six healthy transplant donors. HLA DNA typing was performed by the PCR/SSP method. The frequency of HLA-B62 was significantly higher in patients than in controls. HLA-A2, HLA-A24, HLA-B35, HLA-DRB1*11, and HLA-DRB1*15 were significantly less common in patients than in the control group.     

Double Heterozygosity in the <i>BRCA1/2</i> Genes in a Turkish Patient with Bilateral Breast Cancer: A Case Report

BRCA1 and BRCA2 tumor suppressor genes are responsible for a quarter of hereditary breast cancers. Double heterozygous (DH) pathogenic variant carrier status in these genes is an extremely rare condition, especially in non-Askenazi individuals. We report a woman patient with bilateral breast cancer that carries DH disease-causing variants in BRCA1/2 genes. The 45-year-old patient who was followed up with the diagnosis of metachronous bilateral breast cancer was diagnosed with cancer at the age of 39 and 43, respectively. BRCA1/2 genes of the patient were evaluated using Next-Generation Sequencing. In the patient, the c.2800C>T (p.Gln934Ter) pathogenic variant in BRCA1 and the c.9648+1G>C likely pathogenic variant in BRCA2 were detected as DH. Segregation analysis in family members revealed that her two healthy siblings available for testing were heterozygous for either BRCA1 or BRCA2 variants, but her mother, who had a past diagnosis of ovarian cancer, was heterozygous for both BRCA1 and BRCA2 variants. Germline double heterozygosity in inherited cancer is a rare condition, and as far as we know it is reported for the first time from patient population in Turkey. Large-scale patient series are needed to determine the impact of double heterozygosity on diseases course, such as prognosis and treatment responses.     

Melanocortin 3 receptor gene polymorphism is associated with polycystic ovary syndrome in Turkish population

Polycystic ovary syndrome (PCOS) is a frequent complex disorder with an ill-defined etiology. Genetic factors seem rather effective at the occurrence of the disease, however, the evidence of established various studies results are unsatisfied. We aimed to make a contribution to the genetic baseline of the disease by investigating melanocortin 3 receptor gene polymorphism in affected patients. 101 PCOS patients and 162 age-matched healthy volunteered control subjects recruited to the study. PCOS patients classified according to their BMI class and insulin resistance situation. Anthropometric measurements, physical examination results, laboratory findings, and hormone levels were recorded for each participant and analysis of two SNPs on the MC3R gene; rs3746619 and rs3827103 were performed. Although no significant difference was observed in rs3827103 polymorphism between PCOS patients and controls; rs3746619 polymorphism was determined associated with PCOS in the heritage of dominant (AA + AC) and co-dominant (AA) genotypes. Two polymorphisms did not found related to obesity and insulin resistance in PCOS subgroups analysis. MC3R gene rs 3746619 polymorphism was found associated with PCOS in the Turkish population and may make a contribution to the genetic baseline of the disease.     

Double Heterozygous Mutations in the BRCA2 and ATM Genes: A Case Report and Review of the Literature

IntroductionGermline mutations of the BRCA1 and BRCA2 genes are responsible for about a quarter of hereditary breast cancers (BCs). In this study, we aimed to determine the importance of rare double heterozygous (DH) pathogenic variant carriership in BRCA2and ATM genes in a patient diagnosed with BC and pancreas cancer (PC).Case ReportA 54-year-old female patient was diagnosed with BC at the age of 34 years and with PC at the age of 48 years. The multigene panel and next-generation sequencing technique were used to evaluate the status of the patient''s cancer susceptibility genes. Pathogenic variants c.537dup (p.Ile180Tyrfs*3) in the BRCA2 gene and c.5065C>T (p.Gln1689Ter) in the ATM gene were detected as DH in the patient. Co-segregation analysis was performed on the relatives of the patient using Sanger sequencing.Discussion/ConclusionMultiple primary malignant neoplasms can be encountered more frequently in DH pathogenic variant carriers, and the diagnosis of malignancies can be made at an earlier age through surveillance guided by genetic testing. In this rare case, more patient studies are needed to determine the contribution of DH in BRCA2 and ATM genes to the phenotype.