Study On Relationship Between Genetic Polymorphism Of Il-8 With Pneumoconiosis Sensibility

Objectives Pneumoconiosis is a chronic lung disease due to the inhalation of various forms of dust particles.Different types of dust can resut in different types of pneumoconiosis.Pneumoconiosis is the most common and serious occupational disease in China.According to the end of 2009 year`s data, 18128 new occupational disease had been diagnosed, 14495 of these were pneumoconiosis, coal worker's pneumoconiosis and silicosis account 91.89%.Pneumoconiosis have clear cause and long pathogenesis,and can be diagnosed during exposure to dust. Workers can suffer from pneumoconiosis after departed dust. According to a great deal epidemiological studies of pneumoconiosis, only a few persons suffered from it even they had the same situation of exposure. They had the different ponderance in the group of patients. This fact indicated that the morbidity of pneumoconiosis had the relationship not only with environmental factor but also with individual factor. Dust stimulation can lead lung injury, release inflammatory, stimulate reticular fibers and collagen's hyperplasia.The deposition of immune complex deposition is the basis of changes of pneumoconiosis.Now study more and repute cytokines that have close relationship with the incidence of pneumoconiosis have fibronectin(FN),factor-α,β(TNF-α,β),transforming growth factor (TGF),Interleukin-1(IL-1),Interleukin-6(IL-6) and platelet-derived growth factor(PDGF). IL-8 is a powerful neutrophil chemokine chemotactic factor and activating factor that mainly produced from neutrophils and produced in pathological conditions that including in inflammation, infection, injury, hypoxia, acidosis. IL-8 have a certain degree of chemotaxis on basophils and T cells and it can chemotaxis neutrophils gathered, activate neutrophils release super oxide enzyme and lysosomal enzymes,and produce inflammation,then control the polymorphisms of Interleukin-8. Now we don't find the studies of relationship between the genetic polymorphisms of IL-8 and pneumoconiosis.After strictly matching age of first diagnosis,nationality, the character of exposed to dust and cumulative length of service, we studied the relationship between genetic polymorphism of IL-8 and pneumoconiosis in order to offer the biomarker for susceptibility group of exposure to dust. Subjects and methods 1265 gold mine workers and 2568 coal workers were investigated. All the workers exposed to dust were examined by dorsaventral chest X-ray base on the health check-up. The pneumoconiosis was diagnosed by the Pneumoconiosis Diagnosis Expert Panel, based on the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ70-2009).From them, pneumoconiosis diagnosed were selected as cases, workers exposed dust were selected as controls whose age,the cumulative length of service same as control groups. The cases and control worked in the same jop place.Finally, 213 pneumoconiosis patients were selected as cases,including 101 silicosis patients and 112 coal worker`s pneumoconiosis patients, all them were male and Han nationality. Workers exposed dust were selected as controls.The sex, age had no different between the cases and control groups. The cases and control worked in the same jop place. In the case of informed consent, 1.5 ml venous blood was drawn and anticoagulated with EDTA. The polymorphisms of IL-8 (Met31Arg,781C/T,-251A/T,RA+860) were detected using the method of polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) techniques and PCR. Based on many preliminary experiments, the most adaptive PCR reaction, the restriction enzyme digest and electrophoresis system were determined. We analysed the genotypes with pneumoconiosis by using Pearson′sχ2 test and OR.Results1 General informations213 cases were selected, who were male, Han nationality, stageⅠof pneumoconiosis. Their average age was 54.9±9.4 years, average cumulative length of service was 29.3±6.1 years. 251 controls were male and Han nationality too. Their average age was 54.8±6.3 years, average cumulative length of service was 29.5±4.9 years. There are 101 silicosis patients, their average age was 59.1±8.9 year, average cumulative length of service was 28.0±5.1 years.121 controls were male and Han nationality, their average age was 57.3±8.1 year, average cumulative length of service was 28.1±5.2 years. There are 112 coal worker`s pneumoconiosis patients, their age of first diagnosis was 51.1±8.1 year, average cumulative length of service was 29.8±6.7 years. 130 controls were male and Han nationality, their age was 52.4±1.9 year, average cumulative length of service was 30.6±4.7 years. Differences of age, the beginning year of exposure to dust, cumulative length of service between cases and controls were no significance(P>0.05). The two groups had good comparability.2 The distribution of genotype and allele for IL-8 Met31ArgThe frequencies of GG, GT and TT in IL-8 Met31Arg locus in the pneumoconiosis cases were 0%,14.08% and 85.92% and in the controls were 0.40%,3.59% and 96.37%. The difference were significant (P<0.05). The frequencies of G allele were 7.04% and 92.96% in case and control, the frequencies of T allele were 2.19% and 97.81% in case and control. The difference were significant (P<0.05).Using hierarchy analysis, it was found that there were significant difference in the frequencies of IL-8 Met31Arg genotype between the silicosis cases and control groups (P<0.05). The frequencies of GG, GT and TT in IL-8 Met31Arg locus in the silicosis cases were 0%, 12.87% and 87.13% and in the controls were 0.82%,2.48% and 96.69%. The frequencies of G allele were6.44% and 93.56% in case and control, the frequencies of T allele were 2.07%and 97.93% in case and control. The difference were significant (P<0.05).It was found that there were significant difference in the frequencies of IL-8 Met31Arg genotype between the coal worker`s pneumoconiosis cases and control groups (P<0.05). The frequencies of GG, GT and TT in IL-8 Met31Arg locus in the coal worker`s pneumoconiosis cases were 0%, 15.18% and 84.82% and in the controls were 0%,4.62% and 95.38%. The frequencies of G allele were7.59% and 92.41% in case and control, the frequencies of T allele were 2.31% and 97.69% in case and control. The difference were significant (P<0.05).3 The distribution of genotype and allele for IL-8 -251A/TThe frequencies of TT, AT and AA in IL-8 -251A/T locus in the pneumoconiosis cases were 38.97%,48.83% and 12.20% and in the controls were17.93%,17.93% and 64.14%. The difference were significant (P<0.05). The frequencies of T allele were 63.38%and 53.78% in case and control, the frequencies of A allele were 36.62% and 46.22% in case and control. The difference were significant (P<0.05).Using hierarchy analysis, it was found that there were significant difference in the frequencies of IL-8 -251A/T genotype between the silicosis cases and control groups (P<0.05). The frequencies of TT, AT and AA in IL-8 -251A/T locus in the silicosis cases were 0.59%,49.50% and 9.90% and in the controls were 38.84%,35.54% and 25.62%. The frequencies of T allele were 65.35% and 56.61% in case and control, the frequencies of A allele were 34.61% and 43.39% in case and control. There were not significant difference between cases and controls (P>0.05).It was found that there were significant difference in the frequencies of IL-8 -251A/T genotype between the coal worker`s pneumoconiosis cases and control groups (P<0.05). The frequencies of TT, AT and AA in IL-8 -251A/T locus in the coal worker`s pneumoconiosis cases were37.50%,48.21% and 14.29% and in the controls were33.08%,36.15% and 30.77%. The frequencies of T allele were 61.61% and 51.15% in case and control, the frequencies of A allele were 38.39% and 48.85% in case and control. The difference were significant (P<0.05). 4 The distribution of genotype and allele for IL-8 781C/TThe frequencies of CC,CT and TT in IL-8 781C/T locus in the pneumoconiosis cases were 37.09%,41.31% and 21.60% and in the controls were43.03%,43.03% and 13.94%. The difference were significant (P<0.05).The frequencies of C allele were 57.75% and 64.54% in case and control, the frequencies of T allele were 42.25% and 35.46% in case and control. The difference were significant (P<0.05).Using hierarchy analysis, it was not found that there were significant difference in the frequencies of IL-8 781C/T genotype between the silicosis cases and control groups (P>0.05). The frequencies of CC,CT and TT in IL-8 781C/T locus in the silicosis cases were 38.61%,40.59% and 20.79% and in the controls were 46.28%,40.50% and 13.22%. The frequencies of C allele were 58.91% and 66.53% in case and control, the frequencies of T allele were 41.09% and 33.47% in case and control. There were not significant difference between cases and controls (P>0.05).It was found that there were not significant difference in the frequencies of IL-8 781C/T genotype between the coal worker`s pneumoconiosis cases and control groups (P>0.05). The frequencies of CC,CT and TT in IL-8 781C/T locus in the coal worker`s pneumoconiosis cases were35.71%,41.96% and 22.33% and in the controls were 40.00%,45.38% and 14.62%. The frequencies of C allele were56.70% and 62.69% in case and control, the frequencies of T allele were 43.30% and 37.31% in case and control. There were not significant difference (P>0.05) 5 The distribution of genotype and allele for IL-8 RA+860The frequencies of GG,GC and CC in IL-8 RA+860 locus in the pneumoconiosis cases were 74.24%,23.47% and 3.29% and in the control were 73.31%,20.32% and 6.37%. There were not significant difference (P >0.05).The frequencies of G allele were 84.98% and 83.47% in case and control, the frequencies of C allele were 15.02% and 16.53% in case and control. There were not significant difference (P>0.05).Using hierarchy analysis, it was not found that there were significant difference in the frequencies of IL-8 RA+860 genotype between the silicosis cases and control groups (P>0.05). The frequencies of GG,GC and CC in IL-8 RA+860 locus in the silicosis cases were 75.25%,21.78% and 2.97% and in the control were 80.17%,14.88% and 4.96%. The frequencies of G allele were 86.14% and 87.60 in case and control, the frequencies of C allele were 13.86% and 12.40% in case and control. There were not significant difference between cases and controls (P >0.05).It was found that there were not significant difference in the frequencies of IL-8 RA+860 genotype between the coal worker`s pneumoconiosis cases and control groups (P>0.05). The frequencies of GG,GC and CC in IL-8 RA+860 locus in the coal worker`s pneumoconiosis cases were 71.43%,25.00% and 3.57% and in the control were 66.92%,25.38% and 7.70%. The frequencies of G allele were 83.93% and 79.62% in case and control, the frequencies of C allele were 16.07% and 20.38% in case and control. There were not significant difference (P >0.05)Conclusions1 The genetic polymorphism of IL-8(Met31Arg) relatied to susceptibility of pneumoconiosis.Workers of carrying IL-8(Met31Arg)GT genotype were likely to increase the risk of pneumoconiosis.2 IL-8(-251)related to the development of pneumoconiosis. Workers of carrying IL-8(-251)AA genotype were likely to reduce the risk of pneumoconiosis.3 The genetic polymorphism of IL-8(781C/T) relatied to susceptibility of pneumoconiosis.Workers of carrying IL-8(781C/T)TT genotype were likely to increase the risk of pneumoconiosis.4 The relationship between genetic polymorphism of RA+860 and pneumoconiosis hasn't been found in the study.