SMAD4 gene polymorphisms and genetic susceptibility of coal work's pneumoconiosis

To explore the role of -1C/T single nucleotide polymorphism within Annexin A5 gene in the genetic susceptibility to coal worker's pneumoconiosis (CWP). Four hundred and seventy CWP Han chinese patients and 428 Han chinese controls were enclosed in present case-control study. All subjects were exposed to coal dusts. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the -1C/T SNP in Annexin A5 gene for all subjects. The relationship between the -1C/T SNP in Annexin A5 gene and CWP was analyzed. CT/TT genotype in -1C/T SNP was associated with a significantly decreased risk of CWP, as compared with the CC genotype among subgroups exposed to coal dusts for ≥ 27 years (adjusted OR = 0.65, 95%CI: 0.44 - 0.98, P = 0.039) and patients with CWP at stage II (adjusted OR = 0.55, 95%CI: 0.34 - 0.90, P = 0.028). The results of present study suggest that the Annexin A5 -1C/T polymorphism may be involved in the development of CWP in Han Chinese coal miners.

Objective: To explore the clinical phenotypic characteristics of coal worker's pneumoconiosis for guiding the individualized treatment of various types of patients with coal worker's pneumoconiosis. Methods: Collect clinical data of 121 cases of coal worker's pneumoconiosis in different stages, and select 16 clinical variables (age, smoking index, years of underground dust exposure, stages of pneumoconiosis, types of work, family history, main symptoms, secondary symptoms, CAT score, imaging manifestations, FVC%, FEV(1)/FVC, FEV(1)%, DLCO%, respiratory failure complications, pulmonary heart disease complications) . Principal Component Factor Analysis (PCA) was used to analyze 16 clinical variables of 121 patients with coal worker's pneumoconiosis. Extracted 2 principal components and 8 related variables from 16 clinical variables, then coal worker's pneumoconiosis patients were divided into three types according to CCC values. Variance analysis or χ(2) test were used to analyze the characteristics of these three types of clinical data, then summarized the clinical phenotype composition ratio and clinical data characteristics. Results: The patients with coal worker's pneumoconiosis were initially divided into three types, including 73 cases (60.3%) in type 1, 18 cases (14.9%) in type 2 and 30 cases (24.8%) in type 3. Patients in type 1 are mainly middle-aged, with little damage to lung function and mild clinical symptoms, the imaging manifestations of type 1 patients are mainly diffuse nodules, and the stages of pneumoconiosis are mostly one-stage and second-stage. Patients in type 2 are mainly in middle-aged and elderly patients.the main pulmonary impairment is diffuse function decline. The clinical symptoms are severe and the imaging manifestations are complex. The stages of pneumoconiosis are one, second and third stages. Patients in type 3 are mainly middle-aged and elderly patients, with more pulmonary function impairment (decreased ventilation and diffusion) , severe clinical symptoms, complex imaging manifestations (micro nodules, emphysema, mass shadow, fibrosis) , and those pneumoconiosis stages are mainly in the second and third stages. Conclusion: According to the clinical characteristics, the patients with coal worker's pneumoconiosis were divided into 3 types by cluster analysis method, the treatment plan has certain guiding value in clinical work according to different classifications.

Coal workers' pneumoconiosis (CWP) is characterized by progressive pulmonary fibrosis. Inflammation is crucial in the host response to silica and it contributes to pulmonary fibrosis. Cyclooxygenase-2 is involved in this process. The association between single-nucleotide polymorphisms in cyclooxygenase-2 gene with pneumoconiosis risk was investigated. An association study was conducted by analyzing two single-nucleotide polymorphisms of cyclooxygenase-2 (rs689466 and rs20417) in a case-control study involving 90 patients and 90 healthy individuals (controls). Genotyping was performed by the TaqMan method. The rs689466 AG and GG and rs689466 GC polymorphisms were significantly less frequent in patients than in controls. Cyclooxygenase-2 rs689466 and rs20417 variant genotypes exhibited 21% and 12% decreased CWP risk, respectively. Cyclooxygenase-2 rs689466 and rs20417 polymorphisms were associated with CWP risk.

e13529 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) play a key role in the management of advanced non-small cell lung cancer (NSCLC). Numerous investigations have demonstrated an association between the presence of somatic mutations in EGFR and the sensitivity to gefitinib or erlotinib in NSCLC. Since genetic polymorphisms are more prevalent than mutations in human genome, some of them may be more practical as genetic biomarkers to predict the sensitivity to EGFR-TKIs. The FAS-FASL system plays crucial role in apoptotic signaling in many tumor cells. Here, we assessed the possibility that single nucleotide polymorphisms (SNPs) in FAS and FASL could be used to predict the sensitivity to gefitinib in patients with advanced NSCLC. Methods: Candidate polymorphic loci approach was used to determine the functional polymorphisms. SNPs in the promoter region of the FAS (−1377G/A and −670A/G) and FASL (−844T/C) were assessed in 88 advanced NSCLC patients treated with gefitinib. The Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The association between genotypes and sensitivity to gefitinib was validated by statistical tests. Results: For FAS -1377G/A, the clinical benefit rates (CBR) of gefitinib in advanced NSCLC patients were 31.3%, 61.1% or 74.3% (p = 0.014) in AA, GA or GG genotypes, respectively. For FAS −670A/G, the CBR were 32.0%, 78.0% or 57.9% (p = 0.001) in GG, AG or AA genotypes. For FASL - 844T/C, the CBR were 65.2%, 57.1% or 50% (p = 0.276) in CC, CT or TT genotypes. FAS -670 GG genotype carriers also had a significantly shorter survival time after the treatment of gefitinib than variation allele carriers (AG or AA genotypes), the overall survival time were 26 and 47 months (p = 0.012), respectively. Conclusions: FAS -1377G/A and -670A/G polymorphisms may be predictive for sensitivity to gefitinib in patients with advanced NSCLC. No significant financial relationships to disclose.

BackgroundThe 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.MethodsFive 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.ResultsOur 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).ConclusionOur 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.

Coal worker's pneumoconiosis is caused by the pulmonary deposition of coal dust, including silica particles. Several factors such as chemical composition and physical properties of silica-containing dust, particle size distribution, intensity, and duration of exposure influence the disease development. Genetic factors may also be involved. To define whether HLA-DRB may function as a genetic factor for predisposition to coal worker's pneumoconiosis, we determined DRB1, 3, 4, 5 alleles. For this purpose, DRB typing with sequence-specific oligonucleotide probes in 204 German miners with pneumoconiosis and in 52 German miners without pneumoconiosis was used. The miners had worked under comparable conditions. The frequency of DR8 (1*0801-0804) was increased in patients developing pneumoconiosis during the first 15 years of mining (p = 0.047). The frequency of DR1 (1*0101-0103) was elevated (p = 0.022) and that of DR52 (3*0101, 3*0201, 3*0202, and 3*0301) was reduced (p = 0.026) in miners without pneumoconiosis. Our data show that the presence of DR1 and the absence of DR52 support the resistance to coal worker's pneumoconiosis. Furthermore, DR8 may be involved in the rapid development of coal worker's pneumoconiosis.

Profusion of Opacities in Simple Coal Worker's Pneumoconiosis Is Associated With Reduced Lung Function

ObjectivesSusceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker’s pneumoconiosis (CWP) in recent studies. However, only a few...

To explore the relationship between the polymorphism of Interleukin-1 and the pneumoconiosis susceptibility. Eighty patients with silicosis and 45 with coal workers' pneumoconiosis (CWP) were selected while 125 male workers, Han nationality in the same workplace as the patients were selected as the controls. Between the patients and the control, the differences of age and cumulative length of service were less than five years and two years, respectively. The controls were exposed to dusts but did not suffer from pneumoconiosis. Moreover, the patients and the controls were paired by 1:1. DNA was extracted from leucocytes by the hydroxybenzene chloroform method. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) techniques and PCR were used to examine polymorphism of IL-1alpha (-889), IL-1beta (-511) and IL-1Ra (+2018) and variable number of tandem repeats (VNTR) of IL-1Ra. After the preliminary experiment, the most adaptive PCR reaction, the restriction enzyme digest and electrophoresis system were used. The difference in IL-1alpha (-889) 1/2 + 2/2 between the pneumoconiosis patients and the controls was significant (P < 0.01). The result of conditional Logistic regression showed that heterozygote and allele 2 of IL-1a (-889) were risk factors of pneumoconiosis. The difference in the genotype frequencies of IL-1beta (-511) 1/2 + 2/2, IL-1Ra (+2018) 1/2 + 2/2 and IL-Ra VNTR1/2 + 2/2 between the patients and the controls were not statistically significant (P > 0.05). IL-1alpha (-889) gene polymorphism is related to pneumoconiosis. Workers with IL-1alpha (-889) allele 2 are susceptible to the pneumoconiosis. The relationship between IL-1beta (-511), IL-1Ra (+2018), IL-1Ra VNTR genes polymorphisms and pneumoconiosis are not found.

The aim of the present study was to investigate whether there was any relationship between some DNA N-methyltransferase 1 (DNMT1) polymorphisms and susceptibility to idiopathic sudden sensorineural hearing loss (ISSHL) in ISSHL patients. We investigated 90 patients diagnosed with ISSHL and a control group composed of 75 age- and gender-matched healthy individuals. DNA was extracted from the blood samples by phenol-chloroform method. Polymerase chain reaction and restriction fragment length polymorphism methods were used for the genotyping analysis of 4 regions of DNMT1. For rs2228612 single nucleotide polymorphism (SNP), the frequency of AA, AG, and GG genotypes were 81.4%, 9.3%, and 9.3% in controls and 82.2%, 16.7%, and 1.1% in patients, respectively. We observed a significant decrease in the frequency of GG genotype in patients with ISSHL when compared with controls (p=0.027). The frequency of GG, AG, and AA genotypes for rs2228611 SNP were 20.7%, 49.3%, and 20% in controls and 20%, 47.8%, and 32.2% in patients, respectively. There was a significantly increased frequency of the AA genotype of this SNP in the DNMT1 gene, and we found that individuals with the AA genotype had 2.47 times the risk for ISSHL development than individuals with the GG genotype (p=0.41). The GAA haplotype may constitute 2.66 times the risk for ISSHL disease (OR=2.66, 95% confidence interval: 0.28-25.03). This study's results showed that the AA genotype in rs2228611 polymorphism was a risk factor in ISSHL patients and the GG genotype could be a protective factor in rs2228612 polymorphism.

To investigate the -3826A/G polymorphism in the promoter of the uncoupling protein-1 (UCP1) gene and its relations to obesity in Chinese population. Three hundred and eighty-four subjects (257 non-obese and 127 obese individuals) from a population of Chinese Han nationality in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins A I, A II, B100, C II, C III and E were measured by the RID kits. The frequencies of A and G alleles at -3826A/G site in obese and non-obese groups were 0.508 and 0.492, and 0.467 and 0.533, respectively. It showed no significant difference in allele frequencies between non-obese and obese groups (P > 0.05). In the obese group, subjects with genotype GG had higher serum apo B100 concentrations, and those with genotype AG had higher apo C II and apo C III levels, than those with genotype AA, respectively (P < 0.05). In non-obese male subgroup, subjects with genotype GG had lower serum HDL-C and apo A I levels than those with genotype AA, respectively (P < 0.05), whereas those with genotype AG had lower apo A II levels than those with genotype AA. In addition, in obese males with genotype GG had elevated apo B100 levels compared with those with genotype AA, whereas in obese females with genotype GG had decreased apo AI levels and genotype AG had increased apo C II and apo C III levels compared with those with genotype AG and AA, respectively (P < 0.05). -3826A/G polymorphism in the promoter of the uncoupling protein-1 gene was not associated with obesity in Chinese Han population of Chengdu area. It may be associated with serum HDL-C, apo A I and apo B100 levels in non-obese and/or obese subjects of certain genders.

Background: Despite significant progress made in reducing dust exposures in underground coal miners in the United States, severe cases of coal workers’ pneumoconiosis (CWP), including progressive massive fibrosis (PMF), continue...

BackgroundSeveral studies have reported the association of the SNP rs2414096 in the CYP19 gene with hyperandrogenism, which is one of the clinical manifestations of polycystic ovary syndrome (PCOS). These studies suggest that SNP rs2414096 may be involved in the etiopathogenisis of PCOS. To investigate whetherthe CYP19 gene SNP rs2414096 polymorphism is associated with the susceptibility to PCOS, we designed a case-controlled association study including 684 individuals.MethodsA case-controlled association study including 684 individuals (386 PCOS patients and 298 controls) was performed to assess the association of SNP rs2414096 with PCOS. Genotyping of SNP rs2414096 was conducted by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results.ResultsThe genotypic distributions of rs2414096 (GG, AG, AA) in the CYP19 gene (GG, AG, AA) in women with PCOS (0.363, 0.474, 0.163, respectively) were significantly different from that in controls (0.242, 0.500, 0.258, respectively) (P = 0.001). E2/T was different between the AA and GG genotypes. Age at menarche (AAM) and FSH were also significantly different among the GG, AG, and AA genotypes in women with PCOS (P = 0.0391 and 0.0118, respectively). No differences were observed in body mass index (BMI) and other serum hormone concentrations among the three genotypes, either in the PCOS patients or controls.ConclusionsOur data suggest that SNP rs2414096 in the CYP19 gene is associated with susceptibility to PCOS.

The authors examined the temporal trends of age-specific pneumoconiosis mortality from coal worker's pneumoconiosis (CWP), asbestosis, and silicosis in the United States in 1985-1996. Mortality data were derived from the National Center for Health Statistics multiple causes of death files for the period. Age-specific mortality rates were computed for three age groups (15-44, 45-64, and > or = 65 years) among decedents with mention of CWP, asbestosis, or silicosis. Linear regression analysis was performed to examine the annual changes in age-specific mortality rates, by age group, with each specific condition. The CWP mortality rates declined significantly (p = 0.0001) in the groups 45 years old and older, but not in the age group 15-44. Asbestosis mortality rates declined significantly (p = 0.005) for the age group 45-64, while increasing (p = 0.0001) for those aged 65 years and older. However, in the younger age group 15-44, the rates showed no significant trend. Silicosis mortality rates declined significantly (p = 0.0001) for all groups. The continued occurrence of deaths from CWP, asbestosis, and silicosis among young adults may be the result of high levels of exposure to occupational risks. These results suggest that pneumoconiosis surveillance may help to evaluate the temporal pneumoconiosis mortality patterns in the United States.

Polymorphism of IL6 receptor gene is associated with ischaemic stroke in patients with metabolic syndrome