scholarly journals Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case–control study

2019 ◽  
Vol 76 (3) ◽  
pp. 169-174 ◽  
Author(s):  
Minjie Chu ◽  
Shuangshuang Wu ◽  
Wei Wang ◽  
Yuhui Yu ◽  
Mingjiong Zhang ◽  
...  

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case–control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case–control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility.

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e038926
Author(s):  
Pål Graff ◽  
Johanna Larsson ◽  
Ing-Liss Bryngelsson ◽  
Pernilla Wiebert ◽  
Per Vihlborg

ObjectiveTo determine whether occupational exposure to silica dust is associated with an increased risk of developing sarcoidosis.DesignCase–control study of all individuals between 20 and 65 years of age diagnosed with sarcoidosis (D86) in Sweden between 2007 and 2016. Controls were matched to cases (2:1) based on age, sex and county at the time of diagnosis. A Job Exposure Matrix was used to estimate the occupational silica exposure of all cases and controls.SettingMedical and occupational data from the National Outpatient Register were used to implement a case–control analysis, while the two controls used for each case were selected from the National Register of the Total Population. Information about occupation and time of employment were collected from the Swedish Occupational Register.ParticipantsAll men and women aged 20–65 years old who were diagnosed sarcoidosis (D86) from 2007 to 2016 were included and assigned two controls.Main outcomesSilica dust exposure correlates with an increased risk of developing sarcoidosis in men.ResultsThe prevalence of silica exposure at work was statistically significantly higher among male cases than controls (OR 1.27, 95% CI 1.13 to 1.43). For men of an age of 35 years or younger the correlation seems to be stronger (OR 1.48, 95% CI 1.1 to 1.87) than in older men (OR 1.21, 95% CI 1.05 to 1.39). For men older than 35 with exposure to silica the prevalence of sarcoidosis increased with the exposure time, with an OR of 1.44 (95% CI 1.04 to 2.00) for exposure of more than 10 years.ConclusionsOccupational exposure to silica dust seems to increase the risk of sarcoidosis among men between 20 and 65 years of age. The risk is higher among exposed men 35 years or younger and older men with longer exposure (>6 years).


2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A26.2-A26
Author(s):  
Per Vihlborg ◽  
Pål Graf ◽  
Ing-Liss Bryngelsson

IntroductionSarcoidosis is an inflammatory disease with unknown etiology that involves the formation of granulomas, mainly in the lungs and/or intrathoracic lymph nodes. Hypothesis about the etiology of sarcoidosis are combination of genetic and environmental factors. Previous studies have linked exposure to silica dust with increased risk of sarcoidosis.ObjectA case-control study to investigate the silica exposure among Swedish sarcoidosis cases.MethodsThe data was collected from the National non-primary outpatient care register kept by the Swedish National Board of Health and Welfare. All cases between the age of 20 and 65 with the diagnosis Sarkoidos-D86 according to the International Classification of Diseases, 10th Edition (ICD-10) was included in the study (11 772 cases). The information was matched towards the register for cause of death and the register for emigration.For each case two controls were included matched for age, sex, was resident in the same county, should not be first degree relatives to cases and not have been diagnosed with the investigated disease using the Swedish Central Bureau of Statistics (SCB) multigeneration register. Cases and controls was matched against SCBs occupational registry for work profession. The levels of silica dust exposure were estimated using NOCCA-JEM (Nordic Occupational Cancer study job-exposure matrix) a modified version of the Finnish Information System on Occupational Exposure job-exposure matrix (FINJEM) which is a well-established method of estimating exposure.ResultCases of sarcoidosis have an increased exposure to silica before diagnosis (1.19; 95%  CI 1.1 to 1.30).ConclusionThe increased exposure to silica among sarcoidosis cases suggest that silica can be an environmental factor that contribute to development of sarcoidosis.


BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e034752 ◽  
Author(s):  
Albin Wallden ◽  
Pål Graff ◽  
Ing-Liss Bryngelsson ◽  
Louise Fornander ◽  
Pernilla Wiebert ◽  
...  

ObjectiveTo determine whether occupational exposure to silica dust causes an increased risk of developing Crohn’s disease (CD) and ulcerative colitis (UC).DesignCase–control study of CD (K50) and UC (K51) from 2007 through 2016. Controls were matched to cases (2:1) based on age, sex and county at the time of diagnosis. A job exposure matrix was used to estimate the occupational silica exposure of all cases and controls.SettingMedical and occupational data from the National Outpatient Register were used to implement a case–control analysis, while the two controls used for each case were selected from the National Register of the Total Population.ParticipantsAll men and women aged 20–65 years old who were diagnosed with CD (K50) and UC (K51) during the years of study were included and assigned two controls, resulting in 58 136 cases and 116 272 controls.Main outcomesSilica dust exposure correlates with an increased risk of developing UC in men and CD in women.ResultsThe prevalence of UC was significantly higher in the group exposed to silica dust (OR 1.13, 95% CI 1.06 to 1.21) than in controls, particularly in individuals with over 5 years exposure. When stratified by sex, a significantly increased OR was detected for men (OR 1.33, 95% CI 1.05 to 1.22). This trend was also consistent with longer exposure times. The prevalence of UC was not increased in exposed women. The prevalence of CD was significantly increased among exposed women (OR 1.29, 95% CI 1.01 to 1.65), but not for exposed men.ConclusionsSilica dust exposure correlates with an increased risk of developing UC, especially in men, and the risk seems to increase with the duration and degree of exposure. Conversely, silica dust exposure correlates positively with the risk of developing CD in women.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 973-973
Author(s):  
R. Gonzalez Mazario ◽  
J. J. Fragio-Gil ◽  
P. Martinez Calabuig ◽  
E. Grau García ◽  
M. De la Rubia Navarro ◽  
...  

Background:Cardiovascular disease (CV) is the most frequent cause of death in rheumatoid arthritis (RA) patients. It is well known that RA acts as an independent cardiovascular risk factor.Objectives:To assess the CV risk in RA patients using carotid ultrasonography (US) additionally to the traditional CV risk factors.Methods:A prospective transversal case control study was performed, including adult RA patients who fulfilled ACR/EULAR 2010 criteria and healthy controls matched according to CV risk factors. Population over 75 years old, patients with established CV disease and/or chronic kidney failure (from III stage) were excluded. The US evaluator was blinded to the case/control condition and evaluated the presence of plaques and the intima-media thickness. Statistical analysis was performed with R (3.6.1 version) and included a multivariate variance analysis (MANOVA) and a negative binomial regression adjusted by confounding factors (age, sex and CV risk factors).Results:A total of 200 cases and 111 healthy controls were included in the study. Demographical, clinical and US data are exposed in table 1. Not any difference was detected in terms of CV risk factors between the cases and controls. In both groups a relationship between age, BMI and high blood pressure was detected (p<0.001).Table 1.Table 2.RA basal characteristicsDisease duration (years)16,98 (11,38)Erosions (X-Ray of hands/feet)163 (81,5%)Seropositive (RF/anti-CCP)146 (73%)Extra-articular symptoms44 (22%)Intersticial difusse lung disease10 (5%)Rheumatoid nodules14 (7%)Prednisone use103 (51,5%)Median dose of Prednisone last year (mg)2,34 (2,84)sDMARDsMethotrexate104 (52%)Leflunomide29 (14,5%)Hydroxycloroquine9 (4,5%)bDMARDs89 (44,5%) TNFi41 (20,5%) Abatacept15 (7,5%) IL6i22 (11%) RTX11 (5,5%)JAKi26 (13%) Baricitinib11 (5,5%) Tofacitinib15 (7,5%)DAS 28-ESR3,1 (2,3, 3,9)SDAI7,85 (4,04, 13,41)HAQ0,88 (0,22, 1,5)RF (U/mL)51 (15, 164,25)Anti-CCP (U/mL)173 (22, 340)Patients showed higher intima-media (both right and left) thickness compared to controls (p<0.006). Moreover it was also related to the disease duration and DAS28 score (p<0.001). A higher plaque account was noted in cases(p<0.004) and it was also related to the disease duration (p<0.001).Conclusion:RA implies a higher CV risk. Traditional CV risk factors explains only partially the global risk. These findings support that RA acts as an independent cardiovascular risk factor.Disclosure of Interests:None declared


2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Mahmut Alpayci ◽  
Aysel Milanlioglu ◽  
Veysel Delen ◽  
Mehmet Nuri Aydin ◽  
Huseyin Guducuoglu ◽  
...  

Citrullinated proteins have been suggested to play a critical role in the pathogenesis of multiple sclerosis (MS). Anticyclic citrullinated peptide (anti-CCP) antibody is used in the early diagnosis of rheumatoid arthritis (RA). The objective of this study was to investigate the presence of anti-CCP antibody in patients with MS compared to RA patients and healthy controls. Fifty patients with MS (38 females, 12 males; mean age 36.72 ± 8.82 years), 52 patients with RA (40 females, 12 males; mean age 40.87 ± 10.17 years), and 50 healthy controls (32 females, 18 males; mean age 38.22 ± 11.59 years) were included in this study. The levels of serum anti-CCP antibody were measured using an enzyme-linked immunosorbent assay (ELISA). The results of the study showed that anti-CCP antibody levels were significantly higher in RA patients versus MS or healthy controls(P<0.001). Moreover, anti-CCP antibody was positive in 43 (83%) patients with RA, while it was negative in all MS patients as well as in all healthy controls. Also, no significant correlation was found between the anti-CCP levels and EDSS scores(r=-0.250). In conclusion, the results of this study did not support a positive association between serum anti-CCP antibody and MS.


2013 ◽  
Vol 95 (5) ◽  
pp. 146-155 ◽  
Author(s):  
RUBINA SHARMA ◽  
KAWALJIT MATHAROO ◽  
ROHIT KAPOOR ◽  
HIMANSHI CHOPRA ◽  
AJS BHANWER

SummaryCalpain 10 (CAPN10) variants have been associated with the genetic susceptibility to type 2 diabetes (T2D). In the present case-control study, we analysed the distribution of SNP-19 insertion/deletion (I/D) polymorphism in a total of 607 samples (103 T2D cases and 102 healthy controls) from Brahmin; (100 T2D cases and 100 healthy controls) from Bania and (100 T2D cases and 102 healthy controls) from Jat Sikh ethnic groups of the North-West Indian population. Increased frequency of I allele and II genotype was found in T2D in Brahmin ethnic group [P = 0·003, OR = 2·83 (1·43–5·61 at 95% CI)]. Significant correlation between II genotype and body mass index (BMI) was also observed [P = 0·003, OR = 3·31 (1·52–7·20 at 95% CI)]. No association for the genotypes and alleles was seen in Banias and Jat Sikhs. Our data suggests that SNP-19 I/D variation in the CAPN10 gene is modulated by ethnicity and influences the susceptibility to T2D in the North-West Indian population. We also performed a meta-analysis of relevant studies to assess the validity of this association. Data from 13 case-control studies with 15 760 samples comprising of 8395 T2D cases and 7365 controls were finally analysed. Significant heterogeneity between individual studies was evident in dominant and codominant models. The results of present meta-analysis indicate an association of T2D with carriers of DD genotype of CAPN10 I/D polymorphism. However, further analyses on a larger sample size are required to establish a conclusive association in meta-analysis.


2019 ◽  
Vol 7 (2) ◽  
pp. 59 ◽  
Author(s):  
Ivana Skrinjar ◽  
Valentina Vidranski ◽  
Bozana Loncar Brzak ◽  
Danica Vidovic Juras ◽  
Ana Andabak Rogulj ◽  
...  

It is known that cortisol level increases in stress situations. The aim of the study was to measure the levels of salivary cortisol in patients with oral lichen planus (OLP) and healthy controls. This was a case-control pilot study which included seven patients with reticular (non-symptomatic) OLP, eight patients with atrophic/erosive (symptomatic) OLP, and nine healthy controls. We hypothesized that patients with an atrophic/erosive type of OLP have higher levels of cortisol compared to patients with the reticular type of OLP and healthy controls. In each participant, unstimulated saliva was collected in order to determine cortisol levels by using commercially available ELISA kit. Our results have shown no differences between levels of salivary cortisol in OLP patients and healthy controls. We can conclude that further research with a larger number of OLP patients is needed to determine the correlation between OLP and stress.


2018 ◽  
Vol 108 (3) ◽  
pp. 564-575 ◽  
Author(s):  
Lin Shi ◽  
Carl Brunius ◽  
Ingegerd Johansson ◽  
Ingvar A Bergdahl ◽  
Bernt Lindahl ◽  
...  

ABSTRACT Background Epidemiologic evidence on the association of a healthy Nordic diet and future type 2 diabetes (T2D) is limited. Exploring metabolites as biomarkers of healthy Nordic dietary patterns may facilitate investigation of associations between such patterns and T2D. Objectives We aimed to identify metabolites related to a priori-defined healthy Nordic dietary indexes, the Baltic Sea Diet Score (BSDS) and Healthy Nordic Food Index (HNFI), and evaluate associations with the T2D risk in a case-control study nested in a Swedish population-based prospective cohort. Design Plasma samples from 421 case-control pairs at baseline and samples from a subset of 151 healthy controls at a 10-y follow-up were analyzed with the use of untargeted liquid chromatography-mass spectrometry metabolomics. Index-related metabolites were identified through the use of random forest modelling followed by partial correlation analysis adjustment for lifestyle confounders. Metabolite patterns were derived via principal component analysis (PCA). ORs of T2D were estimated via conditional logistic regression. Reproducibility of metabolites was assessed by intraclass correlation (ICC) in healthy controls. Associations were also assessed for 10 metabolites previously identified as linking a healthy Nordic diet with T2D. Results In total, 31 metabolites were associated with BSDS and/or HNFI (−0.19 ≤ r ≤ 0.21, 0.10 ≤ ICC ≤ 0.59). Two PCs were determined from index-related metabolites: PC1 strongly correlated to the indexes (r = 0.27 for BSDS, r = 0.25 for HNFI, ICC = 0.45) but showed no association with T2D risk. PC2 was weakly associated with the indexes, but more strongly with foods not part of the indexes, e.g., pizza, sausages, and hamburgers. PC2 was also significantly associated with T2D risk. Predefined metabolites were confirmed to be reflective of consumption of whole grains, fish, or vegetables, but not related to T2D risk. Conclusions Our study did not support an association between healthy Nordic dietary indexes and T2D. However, foods such as hamburger, sausage, and pizza not covered by the indexes appeared to be more important for T2D risk in the current population.


2019 ◽  
Vol 161 (5) ◽  
pp. 764-769 ◽  
Author(s):  
Griffin D. Santarelli ◽  
Kent K. Lam ◽  
Joseph K. Han

Objective While urinary leukotriene E4 (uLTE4) is a validated biomarker for the cysteinyl leukotriene pathway, which is central to the pathophysiology of asthma, atopy, and chronic rhinosinusitis (CRS), the contributions of comorbid asthma and atopy to uLTE4 levels in various CRS subtypes have not been previously characterized. We sought to (1) identify reference values for uLTE4 in subjects with and without CRS and (2) determine how the presence of comorbid atopy and asthma affects uLTE4 levels in CRS. Setting Tertiary referral medical center. Subjects and Methods A prospective case-control study was conducted to compare uLTE4 levels between patients with CRS and healthy controls. Urinary LTE4 levels were measured by enzyme immunoassay and were adjusted for urinary creatinine concentrations (pg/mg Cr). Patients with CRS were stratified by the clinical comorbidities to determine normative uLTE4 values for patients with CRS with and without comorbid asthma or atopy. Results A total of 153 patients (mean age, 47.3; 47.1% female) were included in the study. Patients with CRS demonstrated significantly higher concentrations of uLTE4 than healthy controls (1652 vs 1065 pg/mg Cr, P = .032). Within the group of patients with CRS, comorbid asthma also individually correlated with elevated uLTE4 levels (1597 pg/mg Cr, P = .0098). Patients with CRS who did not have comorbid allergy and asthma, in contrast, did not have statistically higher uLTE4 levels than healthy controls (1142 pg/mg Cr, P = .61). Conclusion Urinary LTE4 serves as a noninvasive measure of the inflammatory state in CRS. Comorbid asthma and atopy contribute to elevated uLTE4 levels in CRS.


Sign in / Sign up

Export Citation Format

Share Document