👤 Yutong Sima

Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated. We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors. Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining. Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5. Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions. Show less

Apolipoprotein A5 gene (APOA5) variants are associated with increased plasma triglycerides, a risk factor for the metabolic syndrome (MS), but a correlation with apolipoprotein C3 (APOC3) genotypes is controversial. We investigated the correlation of APOA5 genotypes with plasma apoA5 levels and APOC3 genotypes in MS patients from a Romanian population. APOA5 (-1131T>C, c.56C>G) and APOC3 (-482C>T, -455T>C) genotypes and plasma apoA5 concentration were determined in MS patients and healthy subjects. Results showed higher apoA5 levels in plasma and high density lipoproteins (HDL) from MS patients, carriers of the APOA5 c.56G allele, as compared to MS carriers of APOA5 -1131C allele or the common genotype. ApoA5 levels in plasma and HDL fraction from MS carriers of -1131C and c.56G alleles correlated positively with plasma triglycerides levels and negatively with HDL-cholesterol in MS carriers of c.56G allele. Higher frequencies of APOC3 -482T and -455C alleles were detected in MS patients compared with healthy subjects. We demonstrated the association of APOC3 -482T and -455C with APOA5 -1131C allele, but not with c.56G allele in MS patients. We propose APOA5c.56C>G as a functional polymorphism, whereas APOA5 -1131T>C is not an independent risk factor, being effective only when associated with APOC3 -482T or -455C alleles. Show less

Genetic variation at the apolipoprotein A-V locus, recently discovered proximal to the APOA1/C3/A4 gene cluster, is associated with elevated triglyceride concentrations, a risk factor for atherosclerosis. The goal of our study was to determine the association of two apolipoprotein A-V (APOA5) gene polymorphisms in a group of urban Romanian subjects with the prevalence of the metabolic syndrome. For this purpose, we assayed -1.131T>C and c.56C>G polymorphisms for 279 subjects divided into three groups: a control group, a metabolic syndrome group and a cardiovascular disease group. Then we correlated the minor allele frequencies with body mass index and biochemical parameters. We obtained higher frequency for -1.131C compared to c.56G alleles, both mainly distributed in overweight subjects. Body mass index and triglyceride levels were higher in -1.131C allele carriers in metabolic syndrome patients, but were not significantly different in c.56G carriers compared to those with the native gene. Metabolic syndrome -1.131C homozygotes presented lower high-density lipoprotein cholesterol and higher glucose levels compared to subjects with the native gene. Total cholesterol, low-density lipoprotein cholesterol and insulin were not different between -1.131C or c.56G allele carriers and those with the native gene. Our results demonstrate an independent risk for -1.131T>C APOA5 gene polymorphisms in the development of metabolic syndrome. Show less