ABSTRACT
MALAT1, which is disorderly expressed in the growth, invasion, migration and cancer cell apoptosis, was shown to be associated with normal-tension glaucoma (NTG), a type of optic neuropathy. The haplotype in MALAT1 affects its expression and is correlated with human diseases like normal-tension glaucoma (NTG). However, the underlying detailed mechanism remains unclear. In this study, we aimed to analyse the association between MALAT1 haplotype and the severity of NTG in a molecular level. Quantitative real-time PCR, ELISA and luciferase assays were performed to establish the underlying signalling pathways. RNFL thickness, RA and C/D ratio were calculated for NTG patients. Accordingly, GGGT haplotype was demonstrated to be associated with a decreased risk of NTG. The MALAT1 level in serum of NTG patients carrying GGGT haplotype was significantly decreased compared with NTG patients carrying other haplotypes, along with elevated miR-1 expression and diminished IL-6 expression. NTG patients carrying GGGT haplotype had thicker RNFL and RA, but a smaller C/D ratio. Sequence analysis found potential target sites of miR-1 on MALAT1 and IL-6, and luciferase assay confirmed the inhibitory effect of miR-1 on MALAT1 and IL-6 expression. Meanwhile, MALAT1 also down-regulated miR-1 expression and consequently up-regulated IL-6 expression. This study presented evidence for a regulatory network containing MALAT1, miR-1 and IL-6, and further demonstrated the effect of MALAT1 haplotype on the risk and severity of NTG.
Subject(s)
Alleles , Glaucoma/diagnosis , Glaucoma/etiology , Haplotypes , Intraocular Pressure , RNA, Long Noncoding/genetics , Aged , Biomarkers , Case-Control Studies , Cell Line , Comorbidity , Cytokines/metabolism , Female , Gene Expression Regulation , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Inflammation Mediators/metabolism , Intraocular Pressure/genetics , Male , Middle Aged , Odds Ratio , RNA Interference , Risk Factors , Severity of Illness IndexABSTRACT
OBJECTIVE: To identify the epidemic characteristics and risk factors of an emerging infectious disease-severe fever with thrombocytopenia syndrome (SFTS) in Hubei province. METHODS: Active surveillance program on SFTS was set up in monitoring sites-hospitals, at the township level or above, in Suizhou, Huanggang and Wuhan from January to December, 2010. Specific surveillance program on SFTS was launched across the province in hospitals above the county level. Cases that matched the definition of surveillance case were identified and reported to Centers for Disease Control and Prevention (CDCs). Cases were interviewed and their blood samples collected and detected using PCR and virus isolation. We also conducted serum antibody surveys among healthy population and livestock and surveillance on vector ticks in those high-epidemic areas. RESULTS: 188 cases that matched the definition of surveillance case and 21 deaths were reported in 11 cities, 32 countries and 100 towns in 2010, with an incidence rate of 0.33/10(6). The fatality rate was 11.2%. Data showed that the patients were from hilly areas at the altitude elevated between 28-940 meters. The epidemic period was between April and December with the peak from May to September. The youngest case was an 11-year old, while the eldest was 81 with median age as 56-year old. 95.3% of the patients were farmers. All Patients did not have the history of traveling, two weeks before the onset of SFTS. 93.6% of the patients engaged in different kind of work which was associated with agriculture. 52.8% of the patients had been exposed to ticks. 22.0% of the patients had been bitten by ticks. Skin injury was found in 64.2% of the patients. Samples from 129 cases (68.6%) were collected and detected, with 67.4% of them (87 cases) showed positive by Real time-PCR for SFTS virus. An elevation in antibody titer by a factor of four or evidence of sero-conversion was observed in 11 patients; SFTS virus was isolated from 2 patients. The total antibody positive rates were 3.8%, 55.0% (6/11), 36.7% (2/3) and 80.0% (4/5) respectively in healthy population, dogs, sheep and cows. Ticks from grass, cattle and sheep were detected positive by Real time-PCR. CONCLUSION: Most cases of SFTS in Hubei were infected by SFTS virus, and cases of livestock were infected by SFTS virus. Ticks might serve as an important vector. Skin injury, exposure to tick bites seemed to be the risk factors.
