Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis

BACKGROUND: Endometriosis is a complex disease affecting 10–15% of women at reproductive age. Very few genes are known to be altered in this pathology. RIP140 protein is an important cofactor of oestrogen receptor and many other nuclear receptors. Targeting disruption experiments of nrip1 gene in mice have demonstrated that nuclear receptor interacting protein 1 gene (nrip1), the gene encoding for rip140 protein, is essential for female fertility. Specifically, mice null for nrip1 gene are viable, but females are infertile because of complete failure of mature follicles to release oocytes at ovulation stage. The ovarian phenotype observed in mice devoid of rip140 closely resembles the luteinized unruptured follicle (LUF) syndrome that is observed in a high proportion of women affected of endometriosis or idiopathic infertility. Here we present a preliminary work that analyses the role of NRIP1 gene in humans. METHODS: We have sequenced the complete coding region of NRIP1 gene in 20 unrelated patients affected by endometriosis. We have performed genetic association studies by using the DNA variants identified during the sequencing process. RESULTS: We identified six DNA variants within the coding sequence of NRIP1 gene, and five of them generated amino acid changes in the protein. We observed that three of twenty sequenced patients have specific combinations of amino-acid variants within the RIP140 protein that are poorly represented in the control population (p = 0.006). Moreover, we found that Arg448Gly, a common polymorphism located within NRIP1 gene, is associated with endometriosis in a case-control study (59 cases and 141 controls, p(allele positivity test )= 0.027). CONCLUSION: Our results suggest that NRIP1 gene variants, separately or in combinations, might act as predisposing factors for human endometriosis

Association between symptoms of depression, diabetes complications and vascular risk factors in four European cohorts of individuals with type 1 diabetes - InterDiane Consortium

Aims: To investigate the association between depressive symptomatology and health markers in type 1 diabetes. Methods: Four countries from the InterDiane Consortium had adopted the Finnish Diabetic Nephropathy Study protocol, including the Beck Depression Inventory (BDI). Associations between depression symptomatology, diabetes complications (diabetic nephropathy, proliferative retinopathy, major adverse cardiovascular events [MACE]) and vascular risk factors (metabolic syndrome, body mass index, glycaemic control) were investigated. Results: In a sample of 1046 participants (Croatia n = 99; Finland n = 314; Latvia n = 315; Lithuania n = 318), 13.4% displayed symptoms of depression (BDI score 16) with no statistically significant difference in the prevalence of depression among the cohorts. The highest rates of diabetic nephropathy (37.1%) and proliferative retinopathy (36.3%) were observed in Lithuania. The rates of MACE and metabolic syndrome were highest in Finland. In joint analyses, individuals exhibiting depression symptomatology had higher HbA(1c) (79 vs. 72 mmol/mol, p <0.001) and higher triglyceride concentration (1.67 vs. 1.28 mmol/l, p <0.001), than those without. In the multivariable model, BDI score was positively associated with the presence of diabetic nephropathy, proliferative retinopathy, MACE, and metabolic syndrome and its triglyceride component. Moreover, BDI score was positively associated with the number of metabolic syndrome components, triglyceride concentration, and HbA(1c). Conclusions: Comorbid depression should be considered a relevant factor explaining metabolic problems and vascular outcomes. Causality cannot be inferred from this crosssectional study. (c) 2020 Elsevier B.V. All rights reserved.Peer reviewe

Global and regional myocardial function and outcomes after transcatheter aortic valve implantation for aortic stenosis and preserved ejection fraction

AimTo investigate the effects of transcatheter aortic valve implantation (TAVI) on early recovery of global and segmental myocardial function in patients with severe symptomatic aortic stenosis and preserved left ventricular ejection fraction (LVEF) and to determine if parameters of deformation correlate with outcomes.MethodsThe echocardiographic (strain analysis) and outcome (hospitalizations because of heart failure and mortality) data of 62 consecutive patients with preserved LVEF (64.54±7.97%) who underwent CoreValve prosthesis implantation were examined.ResultsEarly after TAVI (5±3.9 days), no significant changes in LVEF or diastolic function were found, while a significant drop of systolic pulmonary artery pressure (PAP) occurred (42.3±14.9 vs. 38.1±13.9mmHg, P=0.028). After TAVI global longitudinal strain (GLS) did not change significantly, whereas significant improvement in global mid-level left ventricular (LV) radial strain (GRS) was found (-16.71±2.42 vs. -17.32±3.25%; P=0.33; 16.57±6.6 vs. 19.48±5.97%, P=0.018, respectively). Early significant recovery of longitudinal strain was found in basal lateral and anteroseptal segments (P=0.038 and 0.048). Regional radial strain at the level of papillary muscles [P=0.038 mid-lateral, P<0.001 mid-anteroseptum (RSAS)] also improved. There was a significant LV mass index reduction in the late follow-up (152.42±53.21 vs. 136.24±56.67g/m2, P=0.04). Mean follow-up period was 3.5±1.9 years. Parameters associated with worse outcomes in univariable analysis were RSAS pre-TAVI, LV end-diastolic diameter after TAVI, relative wall thickness, and mitral E and E/A after TAVI.ConclusionGlobal and regional indices of myocardial function improved early after TAVI, suggesting the potential of myocardium to recover with a reduced risk for clinical deterioration