Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles during the progression of the MFS. Homozygous mgR mice exhibited MFS-like phenotypic features, such as fragmentation of elastic fibers throughout the vessel wall and were graded into mgR1-4 based on the pathological severity in aortic walls. Comparative gene expression profiling of WT and four mgR mice using microarrays revealed that the changes in the transcriptome were a direct reflection of the severity of aortic pathological features. Gene ontology analysis showed that genes related to oxidation/reduction, myofibril assembly, cytoskeleton organization, and cell adhesion were differentially expressed in the mgR mice. Further analysis of differentially expressed genes identified several candidate genes whose known roles were suggestive of their involvement in the progressive destruction of aorta during MFS. This study is the first genome-wide analysis of the aortic gene expression profiles associated with the progression of MFS. Our findings provide valuable information regarding the molecular pathogenesis during MFS progression and contribute to the development of new biomarkers as well as improved therapeutic strategies.
Animals ; Aorta ; Biomarkers ; Cause of Death ; Cell Adhesion ; Connective Tissue ; Cytoskeleton ; Dilatation ; Elastic Tissue ; Gene Expression ; Gene Expression Profiling ; Gene Ontology ; Humans ; Marfan Syndrome* ; Mice* ; Myofibrils ; Transcriptome*

BACKGROUND: Although osteoporosis is increasing in the elderly population, attempts to analyze the patterns of medical service utilization for osteoporosis are currently not sufficient. The medical services and treatment patterns were investigated using Korea's National Health Insurance claims data, which includes all of the Korean population. METHODS: Through the patient identification algorithm developed by using the administrative claims data in 2007, the adult patients (between 50-100 years) with osteoporosis were identified. The age and gender of the patients who used medical service for osteoporosis were described, in relation with six dichotomous variables. The medical service use patterns such as the type of medical institution and conducting bone mineral density measurement were investigated. RESULTS: The number of patients who used medical service were 1,230,580 (females 89.9%). Sixty one point six percent of the patients were prescribed osteoporosis medicine (indicated for osteoporosis only), and 12.9% of the patients had experienced osteoporotic fracture. The primary medical institutions for treatment were clinics (54.3%), while hospitals were mainly used among the patients with a history of fracture and disease or drug use that may induce secondary osteoporosis. The number of visited medical institutions was 6.4 (as an outpatient) and 0.2 (as admissions) during 6 months. The proportion of patients who conducted bone mineral density measurements within one year before and after the diagnosis of osteoporosis was 66.7% and DXA was the most frequently used densitometry (46.3%). The average number of days for the prescriptions for osteoporosis medicine was 70 days. CONCLUSION: In order to prevent further osteoporotic fractures, appropriate management and treatment should be implemented for osteoporosis patients. To do this, we need to understand the current state of medical service utilization and the treatment of osteoporosis using the National Health Insurance claims data.
Adult ; Aged ; Bone Density ; Densitometry ; Humans ; National Health Programs ; Osteoporosis ; Osteoporotic Fractures ; Prescriptions

PURPOSE: The aim of this study was to develop and validate identification criteria for the cases of osteoporotic hip fracture using the National Health Insurance Database, and we calculated the incidence rate of osteoporotic hip fracture in the Korean population using these criteria. MATERIALS AND METHODS: The criteria to identify osteoporotic hip fracture using a diagnosis code, a procedure code, the type and number of medical service usages and the patients' ages were developed via discussions among experts. These criteria were validated by using a hip fracture cohort in which all the genuine osteoporotic hip fracture patients in the Jeju area were identified by reviewing the registered medical records and radiographs. By applying the identification criteria to the National Health Insurance Database that was accumulated until June 2009, we calculated the incidence rate of osteoporotic hip fracture in patients between 50 and 100 years of age in 2008. RESULTS: The identification criteria had a sensitivity of 93.1% and a positive predictive value of 77.4%. A total of 20,432 osteoporotic hip fracture cases were identified in 2008, and the incidence rate was 15.7 cases per 10,000 persons. The osteoporotic hip fracture incidence rate for females was 20.7 (per 10,000persons), and this was 2.1 times higher than that for the males (9.8case per 10,000persons), and the rates were increased with age. CONCLUSION: The incidence of osteoporotic hip fracture that occurred on a nationwide scale can be more precisely estimated by using the National Health Insurance Database with its comprehensive information on the overall details of treatment as well as the diagnosis codes, and so the incidence of osteoporotic hip fracture can be reliably calculated for each year. The results from this research could be used as evidence in a hip fracture management plan for establishing Korean Health policy.
Cohort Studies ; Female ; Health Policy ; Hip ; Humans ; Incidence ; Male ; Medical Records ; National Health Programs