Analysis of factors associated with family disease burden and correlation with social support among family caregivers of patients with severe mental illnesses.

BACKGROUND: Caregivers are responsible for the home care of family members with severe mental illnesses (SMIs) and their lives are often subject to changes that can create stress and burden. The purpose of this study was to explore the current state of family disease burden and its correlation with social support among family caregivers of SMIs patients. METHODS: Using a random sampling method, a total of 1,108 family caregivers of SMIs patients in community health service centers were selected. A general information questionnaire of family caregivers and patients, the Family Disease Burden Scale, and the Social Support Rating Scale were used. RESULTS: The score of the Family Disease Burden Scale of 1108 family caregivers was 16.57 ± 10.65. Family disease burden was negatively correlated with social support (p < .05). The main influencing factors of family disease burden were average annual family income, duration of illness, distance to medical care, risk of unpredictable behavior, social support, caregiver-patient relationship, gender, and comorbid chronic conditions (p < .05). CONCLUSION: Family caregivers of SMIs patients have a relatively low level of caregiver-perceived social support. Interventions to enhance perceived social support could help maintain the health of family caregivers and improve the quality of family care.

The association of LAMB1 polymorphism and expression changes with the risk of coal workers' pneumoconiosis.

BACKGROUND: Pneumoconiosis is a serious occupational disease worldwide, which is characterized by irreversible and diffuse lung fibrotic lesions. Laminin beta 1(LAMB1) is widely expressed in tissues and it is crucial for both lung morphogenesis and physiological function. In this study, we explored the association between LAMB1 rs4320486 and risk of pneumoconiosis in a Chinese population, as well as its mechanisms. METHODS: In this case-control study, 600 CWP patients and 605 controls were genotyped for the LAMB1 rs4320486 polymorphism using TaqMan methods. Luciferase reporter assay was used to assess the LAMB1 transcriptional activities. The protein levels in cells and tissues were detected by western blot, and mRNA levels were determined by qRT-PCR. RESULTS: Logistic regression analysis revealed that individuals with LAMB1 rs4320486 CT/TT genotypes had a significantly decreased risk of CWP (adjusted OR = 0.78, 95%CI = 0.64-0.94), compared with individuals with CC genotypes. Luciferase assays showed that the LAMB1 rs4320486(C > T) substitution could decrease the expression of LAMB1. Compared with normal groups, mRNA levels of LAMB1 were up-regulated in lung tissues of patients with pulmonary fibrosis. Additionally, expressions of LAMB1 and α-SMA were enhanced progressively, along with the development of lung fibrosis, while E-cadherin decreased. CONCLUSIONS: In this study, the functional LAMB1 rs4320486 mutation was associated with a decreased risk of CWP in a Chinese population, probably owing to the reduced activity of LAMB1 transcription. LAMB1 expression was increased in the progress of lung fibrosis, which suggests that LAMB1 may affect the initiation and progression of pneumoconiosis, or serve as a potential biomarker of pneumoconiosis for diagnosis and genetic susceptibility.

[Gene variance in microsomal epoxide hydrolase and the susceptibility of coal workers' pneumoconiosis].

OBJECTIVE: To explore whether the tagging single nucleotide polymorphisms (SNPs) within EPHX1 gene were involved in the genetic susceptibility to coal worker's pneumoconiosis (CWP) by case-control study. METHODS: This study consisted of 697 CWP patients and 694 controls. All the subjects were Han Chinese, underground coal miners and recruited from coal mines of Xuzhou Mining Business Group Co Ltd.. The venous blood samples were obtained from all subjects and extracted genome DNA from the isolated leucocytes. Three SNPs were selected from the HapMap and the genotyping was done by the TaqMan method with the ABI 7900HT Real Time PCR system. RESULTS: The Single SNP analyses showed that the genotype frequencies of EPHX1 (rs2234922) was significantly associated with decreased risk of CWP under co-dominant model (OR = 0.22, 95% CI = 0.06~0.79, P = 0.020), recessive model (OR = 0.23, 95% CI = 0.06~0.82, P = 0.023), and addictive model (OR = 0.75, 95% CI = 0.58~0.96, P = 0.022). The further stratification analysis showed that the risk of CWP will significantly decreased in non-smoking groups (OR = 0.10, 95% CI = 0.01~0.83, P = 0.033). CONCLUSIONS: Our results suggest that individuals with the EPHX1 (rs223492) GG genotype was associated with a dereased risk of CWP, and it has a protective effect on the developing CWP.

Associations of MMP1, MMP2 and MMP3 Genes Polymorphism with Coal Workers' Pneumoconiosis in Chinese Han Population.

Coal workers' pneumoconiosis (CWP) has been associated with abnormalities in the extracellular matrix remodeling, as well as aberrant matrix metalloproteinases (MMPs) in lung tissues. We investigated the association of three functional polymorphisms in MMP gene promoters (MMP1 rs1799750, MMP2 rs2285053 and MMP3 rs522616) with the risk of CWP. A total of 693 CWP cases and 690 controls were included in a case-control study. Genotype analysis was performed by the TaqMan method. Statistically significant differences were found in distributions of MMP3 rs522616 under a recessive model (p = 0.047) between CWP cases and controls. In the stratification analysis, individuals with MMP3 rs522616 GG genotype decreased the risk of CWP (adjusted OR = 0.72, 95% CI = 0.52-0.99) compared to those with AA/AG genotype obviously, particularly among subgroups of no smokers (adjusted OR = 0.64, 95% CI = 0.41-1.00). Furthermore, serum MMP3 protein levels measured with enzyme-linked immune-sorbent assay in the control group was significantly lower than that in the CWP groups (p = 0.02). Extremely lower MMP3 among subjects with the rs522616 GG or AG genotype compared with the AA genotype carriers (p < 0.05, p < 0.01 respectively) in the normal serum. These findings indicate that the MMP3 rs522616 polymorphism may contribute to the etiology of CWP in the Chinese population and MMP3 might be a potential diagnostic biomarker for CWP, additional independent studies are warranted to validate our findings in different populations as well as in a larger series.

The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis.

To identify microRNAs (miRNAs, miRs) with potential roles in lung fibrogenesis, we performed genome-wide profiling of miRNA expression in lung tissues from a silica-induced mouse model of pulmonary fibrosis using microarrays. Seventeen miRNAs were selected for validation via qRT-PCR based on the fold changes between the silica and the control group. The dysregulation of five miRNAs, including miR-21, miR-455, miR-151-3p, miR-486-5p and miR-3107, were confirmed by qRT-PCRs in silica-induced mouse model of pulmonary fibrosis and were also confirmed in a bleomycin (BLM)-induced mouse lung fibrosis. Notably, miR-486-5p levels were decreased in the serum samples of patients with silicosis, as well as in the lung tissues of patients with silicosis and idiopathic pulmonary fibrosis (IPF). In addition, as determined by luciferase assays and Western blotting, SMAD2, a crucial mediator of pulmonary fibrosis, was identified to be one of target genes of miR-486-5p. To test the potential therapeutic significance of this miRNA, we overexpressed miR-486-5p in animal models. At day 28, miR-486-5p expression significantly decreased both the distribution and severity of lung lesions compared with the silica group (P < 0.01). In addition, miR-486-5p had a similar effect in the BLM group (P < 0.001). These results indicate that miR-486-5p may inhibit fibrosis.

Associations of MMP-7 and OPN gene polymorphisms with risk of coal workers' pneumoconiosis in a Chinese population: a case-control study.

BACKGROUND: The matrix metalloproteinase-7 (MMP-7) and osteopontin (OPN) are both multifunctional proteins with roles in inflammation, cell proliferation, tissue remodeling and so on, implicated in the pathogenesis of numerous conditions including pulmonary fibrosis. In this study, we investigated the associations between the potential functional polymorphisms in MMP-7 and OPN and the risk of coal workers' pneumoconiosis (CWP) in a Chinese population. METHODS: Four polymorphisms (rs10502001 in MMP-7, rs1126772, rs11728697 and rs9138 in OPN) were genotyped and analyzed in a case-control study of 697 CWP and 694 control subjects. RESULTS: Our results revealed that three single nucleotide polymorphisms (SNPs, MMP-7 rs10502001, OPN rs1126772 and OPN rs11728697) were associated with increased risk of CWP under a recessive model (adjusted odds ratio [OR]=1.80, 95% confidence interval [CI]=1.01-3.20, p=0.045 for MMP-7 rs10502001; adjusted OR=2.09, 95% CI=1.17-3.72, p=0.013 for OPN rs1126772; adjusted OR=2.48, 95% CI=1.37-4.51, p=0.003 for OPN rs11728697). Additionally, a combined effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (Ptrend=0.003). Furthermore, logistic regression analysis revealed no significant interaction between SNPs and smoking status on CWP risk. CONCLUSIONS: Our results indicate that three functional SNPs (MMP-7 rs10502001, OPN rs11728697 and OPN rs1126772) are associated with an increased risk of CWP in a Chinese population.

Polymorphisms in interleukin 17A gene and coal workers' pneumoconiosis risk in a Chinese population.

BACKGROUND: The interleukin 17A (IL-17A) which is located on chromosome 6p and has been linked to chronic inflammation, is an important candidate gene conferring coal workers' pneumoconiosis (CWP). The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL-17A and CWP in a Chinese population. METHODS: We conducted a case-control study to investigate the role of four common SNPs in the IL-17A gene, and evaluated the relationship between these four SNPs and dust-exposure year, tobacco smoking and stages of CWP. A total of 1391 subjects was enrolled in this study, including 694 subjects in control group and 697 in case group. TaqMan based qRT-PCRs were taken to genotype rs2275913, rs3748067, rs4711998, and rs8193036 within the IL-17A gene. Luciferase assays were used to determine the effects of rs8193036 C > T alleles on the expression of IL-17A. RESULTS: Unconditional logistic regression analysis showed that the genotypes of rs3748067 AA (adjusted OR = 0.43, 95 % CI = 0.23-0.83) and rs8193036 TT (adjusted OR = 0.59, 95 % CI = 0.40-0.86) were associated with a decreased risk of CWP, particularly among subgroups of smokers (adjusted OR =0.34, 95 % CI = 0.13-0.86 for rs3748076; adjusted OR = 0.41, 95 % CI = 0.23-0.71 for 8193036) and CWP cases with stage I (adjusted OR = 0.45, 95 % CI = 0.21-0.98 for rs3748076; adjusted OR = 0.46, 95 % CI = 0.28-0.74 for 8193036). Furthermore, the polymorphism of rs3748067 significantly reduced the CWP risk among cases with over 27 years of dust exposure (adjusted OR = 0.42, 95 % CI = 0.18-0.97). The luciferase assays in two cell lines showed that the rs8193036 C > T substitution could reduce the expression of IL-17A, which was consistent with the findings of our association study. CONCLUSIONS: The rs3748067 G > A and rs8193036 C > T polymorphisms decrease CWP risk. These findings could be helpful in identifying individuals at decreased risk for CWP and further studies are warranted to validate them.

GITR promoter polymorphism contributes to risk of coal workers' pneumoconiosis: a case-control study from China.

BACKGROUND: Glucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein (GITR) mainly affects the functions of effector T cells and regulatory T cells thus it may influence various diseases. Coal workers' pneumoconiosis (CWP) is a serious occupational disease worldwide. In the present study, we examined the association between the functional polymorphisms in GITR and risk of CWP in a Chinese population. METHODS: An association study analyzing three polymorphisms (rs3753348, rs2298213, and rs11466668) in GITR were performed in a case-control study including 693 patients with CWP and 690 controls. Genotyping was carried out by Taqman method. RESULTS: The GITR rs3753348 GG/GC genotypes significantly enhanced the risk of CWP (adjusted OR=1.32, 95%CI=1.02-1.71), compared with the CC genotype, particularly among subgroups of long exposure years (adjusted OR=1.47, 95%CI=1.06-2.04) and non-smokers (adjusted OR=1.45, 95%CI=1.01-2.09). Moreover, the polymorphism was significantly associated with risk for CWP cases with stage II. CONCLUSIONS: This is the first report revealing an association between the GITR rs3753348 polymorphism and CWP, and our results suggest that the GITR rs3753348 polymorphism may be involved in the development and susceptibility of CWP.

Polymorphisms in SPARC and coal workers' pneumoconiosis risk in a Chinese population.

BACKGROUND: The SPARC is a crucial matricellular protein and may influence the course of various diseases like tumor metastasis and fibrosis. In the present study, we investigated the association between the potential functional polymorphisms in SPARC and coal workers' pneumoconiosis (CWP) risk in a Chinese population. METHODS: Five potentially functional polymorphisms (rs1059279, rs1059829, rs1053411, rs2304052 and rs4958281) in SPARC were genotyped and analyzed in a case-control study including 697 CWP cases and 694 controls. The genotyping was used by the TaqMan method with the ABI 7900HT Real Time PCR system. RESULTS: Our results revealed that three SNPs (rs1059279, rs1059829, rs1053411) were significantly associated with increased risk of CWP under an additive model (OR = 1.35, 95%CI = 1.06-1.71, P = 0.015 for rs1059279; OR = 1.20, 95%CI = 1.03-1.39, P = 0.021 for rs1059829; OR = 1.31, 95%CI = 1.03-1.65, P = 0.025 for rs1053411). In the stratification analysis, significant associations were observed between each of these three SNPs and patients with 0-20 pack-years of smoking (OR = 1.73, 95%CI = 1.21-2.45 for rs1059279; OR = 1.48, 95%CI = 1.07-2.05 for rs105982; OR = 1.58, 95%CI = 1.13-2.22 for rs1053411). Furthermore, the association between rs1059279 and CWP risk remained significant among subjects with over 27 years of exposure (OR = 1.27, 95%CI = 1.03-1.56, P = 0.023). In the combined analysis of these five polymorphisms, individuals with multiple risk alleles had a higher risk of CWP (Ptrend = 0.015). CONCLUSION: Our results indicate that three functional SPARC SNPs are associated with an increased risk of CWP in a Chinese population. Further functional research and validation studies with diverse populations are warranted to confirm our findings.

MUC5B promoter polymorphisms and risk of coal workers' pneumoconiosis in a Chinese population.

Coal workers' pneumoconiosis (CWP) is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Genetic variations have been recognized to be involved in the multi-factorial susceptibility to CWP, and MUC5B is a candidate lung fibrosis susceptibility gene. In the present study, we investigated possible genetic associations between three single nucleotide polymorphisms in MUC5B promoter region and CWP in a case-control study including 686 CWP patients and 680 controls. Genotyping was carried out by TaqMan method. Only rs2672794 allele and genotype frequencies distributions were significantly different between CWP patients and controls (P = 0.017 and 0.046 for allele and genotype, respectively). The MUC5B rs2672794 CC genotype was associated with a significantly increased risk of CWP, compared with the TT genotype. Moreover, individuals with TC/CC genotype had an obviously increased risk of CWP than those with TT genotype, particularly among subgroups of dust exposure <27 years and smokers. This is the first report showing an association between the MUC5B rs2672794 polymorphism and CWP, and our results suggest that MUC5B rs2672794 CC genotype could increase the risk of CWP. Further studies are warranted to confirm our findings.

[Regulatory effect of miR-149 on interleukin-6 expression in silica-induced pulmonary fibrosis].

OBJECTIVE: To investigate the regulatory effect of miR-149 on interleukin-6 (IL-6) expression in silica-induced pulmonary fibrosis. METHODS: A mouse model of pulmonary fibrosis was established using silica dust; the level of miR-149 in the lung tissues of mice with silica-induced pulmonary fibrosis was measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein expression of IL-6 was measured by immunohistochemistry and Western blot. Type II alveolar epithelial cells (A549) and bronchial epithelial cells (HBE) were exposed to silica dust to establish a model; the level of miR-149 was measured by qRT-PCR, while the protein expression of IL-6 was measured by Western blot. A549 cells were transfected with miR-149 mimics and inhibitor in vitro, and the cellular expression of IL-6 was measured by Western blot. Serum samples from patients with coal workers' pneumoconiosis were examined by double-antibody sandwich ELISA to measure the protein expression of IL-6. RESULTS: At three time points after silica treatment, the miR-149 expression in lung tissues was significantly down-regulated while an evident increase in IL-6 expression was observed in lung tissues (P < 0.01). Silica-stimulated epithelial cell (A549 and HBE) had up-regulated IL-6 expression and down-regulated miR-149 expression (P < 0.01). Increased levels of miR-149 attenuated IL-6 expression, whereas adverse results were found when miR-149 was inhibited. Compared with that in control group, serum level of IL-6 was significantly increased in patients with stage II and III coal workers' pneumoconiosis (P < 0.01). CONCLUSION: Down-regulation of miR-149 and up-regulation of IL-6 might be involved in the progression of silica-induced pulmonary fibrosis; miR-149 could negatively regulate IL-6 expression.