ABSTRACT
BACKGROUND AND AIMS: Type I hyperlipoproteinemia, also known as familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disorder caused by variants in LPL, APOC2, APOA5, LMF1 or GPIHBP1 genes. The aim of this study was to identify novel variants in the LPL gene causing lipoprotein lipase deficiency and to understand the molecular mechanisms. METHODS AND RESULTS: A total of 3 individuals with severe hypertriglyceridemia and recurrent pancreatitis were selected from the Lipid Clinic at Sahlgrenska University Hospital and LPL was sequenced. In vitro experiments were performed in human embryonic kidney 293T/17 (HEK293T/17) cells transiently transfected with wild type or mutant LPL plasmids. Cell lysates and media were used to analyze LPL synthesis and secretion. Media were used to measure LPL activity. Patient 1 was compound heterozygous for three known variants: c.337T > C (W113R), c.644G > A (G215E) and c.1211T > G (M404R); patient 2 was heterozygous for the known variant c.658A > C (S220R) while patient 3 was homozygous for a novel variant in the exon 5 c.679G > T (V227F). All the LPL variants identified were loss-of-function variants and resulted in a substantial reduction in the secretion of LPL protein. CONCLUSION: We characterized at the molecular level three known and one novel LPL variants causing type I hyperlipoproteinemia showing that all these variants are pathogenic.
Subject(s)
Hyperlipoproteinemia Type I/genetics , Lipoprotein Lipase/genetics , Mutation , Adult , Aged , Female , Genetic Predisposition to Disease , HEK293 Cells , Heterozygote , Homozygote , Humans , Hyperlipoproteinemia Type I/blood , Hyperlipoproteinemia Type I/diagnosis , Hyperlipoproteinemia Type I/enzymology , Hypertriglyceridemia/blood , Hypertriglyceridemia/enzymology , Hypertriglyceridemia/genetics , Lipids/blood , Lipoprotein Lipase/metabolism , Male , Middle Aged , Pancreatitis/blood , Pancreatitis/enzymology , Pancreatitis/genetics , Phenotype , Recurrence , TransfectionABSTRACT
PURPOSE: The objective of our study was to evaluate the presence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in a human immunodeficiency virus (HIV)-infected outpatient population and to further investigate the role of highly active antiretroviral therapy (HAART) and other possibly associated risk factors. METHODS: We consecutively enrolled in a cross-sectional study HIV-infected patients and HIV-negative age, sex and smoking status matched controls. All participants completed a questionnaire for pulmonary symptoms and underwent a complete spirometry. RESULTS: We enrolled 111 HIV-infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected patients had a significantly higher prevalence of any respiratory symptom (p = 0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had a significantly higher prevalence of COPD in respect of HIV-negative controls (p = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002) lower forced expiratory volume at one second (FEV1) and FEV1/forced vital capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung capacity (TLC) was significantly higher (p = 0.018). In the multivariate analysis, significant predictors of respiratory symptoms were current smoking [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89-32.12] and previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13-17.13), whereas the only significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77-19.96). HAART receipt was not associated with respiratory symptoms nor with COPD. CONCLUSIONS: We evidenced a high prevalence of respiratory symptoms and COPD among HIV-infected patients. HIV infection, current cigarette smoking and previous bacterial pneumonia seem to play a significant role in the development of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk HIV-infected patients should be screened for COPD to early identify those who may need specific treatment.
Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/virology , Adult , Case-Control Studies , Comorbidity , Confidence Intervals , Cross-Sectional Studies , Female , Forced Expiratory Volume , HIV Infections/drug therapy , HIV Protease Inhibitors/pharmacology , Humans , Lung/pathology , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prevalence , Risk Factors , Ritonavir/pharmacology , Smoking/adverse effects , Spirometry , Surveys and Questionnaires , Total Lung CapacityABSTRACT
Primary spontaneous coronary artery dissection occurs rarely. Compared to usual acute coronary syndromes, it occurs in relatively young people, particularly in women in the peripartum or early post-partum period. The etiology of spontaneous coronary artery dissection remains unclear; there have been less than 150 cases reported in the literature, and only 28 cases documented in the left main coronary artery. This article reports the clinical course of a patient with primary spontaneous left main coronary artery dissection who was treated with coronary artery bypass grafting after clinical steadiness.
