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Clinical Characteristics Of Chronic Osteomyelitis,Diagnostic Values Of Different Serum Inflammatory Biomarkers And Associations Between Single Nucleotide Polymorphisms And Risk Of Development Of The Disease

Posted on:2017-05-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:N JiangFull Text:PDF
GTID:1364330488480469Subject:Surgery (bone)
Abstract/Summary:PDF Full Text Request
In recent years,with the rapid development of the economy in our country,the incidence of industry,life and traffic accidents is increasing.The number of patients that suffer from higher energy by open fractures and that receive internal fixations for closed fractures is also rising.According to a recent epidemiological survery regarding the trends of osteomyelitis,the incidence of osteomyelitis in American population had increased from 11.4/100,000 person-years of the decade from the year 1969 to 1979 to 24.4/100,000 of the decade from the year 2000 to 2009.Chronic osteomyelitis,defined as pathogens or autoinflammatory associated chronic and persistent bone infections(more than 10 weeks),is characterized by inflammation associated bone destruction and simultaneously,the formation of new bone around the infection site.Previous studies had indicated that the incidence of chronic osteomyelitis is affected by several factors including fracture type,degree of soft tissue injury,pathogen type,host immune status and treatment strategies.Take orthopaedic implant associated infections as an example,the incidence ranges from 0.4%to 16.1%,with an average of 5%.The rate of such infection secondary to closed fractures is about 1%to 2%.However,the average rate following open fractures exceeds 30%,ranging from 1%to 55%.According to Gustilo-Anderson classification for open fractures,the incidence of infection for type I is 0%to 9%,1%to 12%for type II and 9%to 55%for type III.Therefore,the more serious of the injury,the higher risk of infection may occur.Currently,chronic osteomyelitis stills to be one of the most challenging disorders for orthopaedists due to its long disease course,complex in treatment and higher risks of recurrence and disabilities.In addition to the above features,great differences were also found regarding the clinical characteristics of chronic osteomyelitis among different studies,which are probably associated with multiple factors including geography,ethnicity,economy and culture.Previous studies had demonstrated that the disease is more frequent in developing countries,which is probably associated with economy status,life styles and level of medical services.It is believed that chronic osteomyelitis used to be a sequelae of acute hematogenous osteomyelitis without prompt or appropriate therapy.However,growing evidence shows that etiology percentages of the disease following trauma and diabetes are continuously increasing.Additionally,apart from bacteria that can cause infection,virus,protozoan and fungus can also result in chronic osteomyelitis.Moreover,biofilm infections are becoming more frequent with widespread use of orthopaedic implants.Due to the above mentioned factors,great differences exist regarding clinical features of chronic osteomyelitis among different countries and different ethnicities.Although previous studies had reported clinical features of the disease,currently,limited report is found regarding clinical features of chronic osteomyelitis in Chinese population with a larger sample size.Diagnosis of chronic osteomyelitis consists of clinical signs and symptoms,medical history,imaging tests,laboratory tests and histopathological tests.As an important aspect of laboratory tests,detection of serum levels of inflammatory biomarkers plays a significant role in initial judgment of infection.A study indicated that predicted probability of infected nonunion achieved 100%using a combination of elevated levels of white blood-cell count(WBC),erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP).Additionally,another study investigated metabolism characteristics of different inflammatory markers in patients with bone infections.Outcomes revealed that serum levels of WBC,CRP and procalcitinin(PCT)were back to near normal value at one week after initial antibiotic treatment.However,it would take at least 3 months for ESR.Therefore,they recommended the use of ESR as a follow-up indicator to assess clinical efficacy.After retrospective review of previous reports,we found that although many studies reported diagnostic roles of inflammatory markers for osteoarticular infections,most of the studies focused on acute phase infections or periprosthetic joint infections.Limited studies reported these aspects in patients with chronic osteomyelitis.In addition,few studies addressed serum interleukin-6(IL-6)and tumor necrosis factor-a(TNF-a)for diagnosis of chronic osteomyelitis.With respect to the risk of development of chronic osteomyelitis,previous studies had explored potential associations from perspective of single nucleotide polymorphism(SNP).SNP is defined as polymorphism of nucleic acid caused by change of a single nucleotide base sequence.It is a phenomenon that differences only exist in a single nucleotide base sequence in the same chromosome or nucleotide sequences of the same site among different individuals.Valle-Garay found tPA Alu I/D polymorphism(rs4646972)is associated with increased risk of osteomyelitis in Spanish.Their team also found matrix metalloprotease-1(MMP-1)(-1607 1G/2G)polymorphism(rs1799750),nitric oxide synthase3(NOS3)27-bp repeat,intron 4 polymorphism and toll-like receptor 4(TLR4)polymorphism(rs4986790)are associated with the risk of developing of chronic osteomyelitis.In addition,Tsezou et al.indicated that IL-la-889-C/T(rs1800587),IL-4-1098-G/T(rs2243248),-590-C/T(rs2243250)and IL-6-174-G/C(rs1800795)polymorphisms increase the susceptibility to chronic osteomyelitis in Greek population.The above mentioned studies demonstrated that SNP is closely related to the risk of developing of chronic osteomyelitis.However,after reviewing previous reports,we found that the number of such SNP studies for chronic osteomyelitis is still limited and most of the studies were performed in European population.Currently,there still lacks reports for potential SNP associations with osteomyelitis in Chinese population.Based on potential geographical and ethnical differences,we inferred that different SNP outcomes may exist between Chinese population and western populations.Based on the above analysis,our study included the following four sections.The first section was clinical characteristics of extremity chronic osteomyelitis.In this section,clinical features of extremity chronic osteomyelitis,clinical features among different types of chronic osteomyelitis and treatment strategies in a single center in Southern China were reviewed.The second section was diagnostic values of different serum inflammatory biomarkers.In this section,we investigated diagnostic values of 6 different inflammatory biomarkers(WBC,ESR,CRP,PCT,IL-6 and TNF-a)for chronic osteomyelitis,serum levels of inflammatory biomarkers between/among different gender,age,osteomyelitis type,infection site number,culture outcome,pathogen number and injury feature groups and their influencing factors.The third section focused on associations of TNF family polymorphisms with risk of developing chronic osteomyelitis.In this section,we explored potential associations of 7 TNF SNPs with susceptibility to osteomyelitis,traumatic and non-traumatic osteomyelitis.The fourth section focused on links between IL family polymorphisms and chronic osteomyelitis.In this section,we investigated potential links between 24 IL SNPs and the risk of development of osteomyelitis,traumatic and non-traumatic osteomyelitis.Part One:Clinical Characteristics of Chronic OsteomyelitisObjectives:To review clinical characteristics,clinical features among different types of chronic osteomyelitis and treatment of the disease in a single center in Southern China.Methods:Clinical data were collected in patients who had sought medical attention to the Department of Orthopaedics and Traumatology,Nanfang Hospital between January 2010 and October 2015 with definite diagnosis of extremity chronic osteomyelitis.Data collected included patient ID number,admission number,name,gender,age at diagnosis,type of chronic osteomyelitis(Waldvogel classification),injury or no injury,injury feature,open or closed injury,multiple or single site infection,infection site,intraoperative culture outcome,surgical procedures,and intravenous antibiotic strategies during hospitalization.Statistical analysis:Statistical analysis was conducted using the SPSS 13.0 software(SPSS Inc,Chicago,IL,USA).The distribution of continuous data was evaluated using the Kolmogorov-Smirnov test.Continuous variables were expressed as mean ± standard deviation(M ± SD)or median with IQR depending on data distribution.For normally distributed data,Student t test or one-way analysis of variance(ANOVA)was used to compare differences between 2 different groups or among more than 2 groups.Otherwise,Mann-Whitney U test or Kruskal-Wallis H test was used.Dichotomous variables were expressed as percentages and Chi-square test was used to compare rates among different groups.A P value of<0.05 was defined as statistical difference.Results:A total of 482 cases comprising 377 males and 105 females were included,with a gender ratio of 3.59.The median age for the first diagnosis was 42 years with interquartile range(IQR)of 24 to 54 years.The most frequent type was traumatic osteomyelitis(331 cases,68.67%),which was mostly caused by open injury(211 cases,63.75%)and during a traffic accident(116 cases,35.04%).Single site infection accounted for 81.95%(395 cases),with the most common site of tibia(163 cases,41.26%),femur(102 cases,25.76%)and calcaneus(42 cases,10.61%).The positive rate of intraoperative culture was 68.99%(247/358),79.35%(196/247)of which was monomicrobial infection.The most frequently detected pathogen was Staphylococcus aureus(65 cases,33.16%),followed by Pseudomonas aeruginosa(38 cases,19.39%)and Enterococcus faecalis(12 cases,6.12%).Significant differences were found regarding sex ratio(P = 0.000),median age at diagnosis(P =0.000),side ratio(P = 0.000),proportion of multiple infection sites(P = 0.000)and positive rate of pathogen culture(P = 0.000)among different types of chronic osteomyelitis(traumatic,hematogenous and diabetic foot osteomyelitis).Focus debridement was the most frequently used surgical procedure(39.00%).Among the 283 patients who were received follow-ups for at least 12 months,no infection recurrence was found in 220 patients,with a total cure rate of 77.74%.The overall cure rate by surgical interventions was 82.88%(213/257),with a total amputation rate of 16.39%(79/482).The most commonly used intravenous antibiotic was cephalosporins and the median duration for intravenous use was 14 days with IQR of 8 to 23 days.Conslusions:(1)Extremity chronic osteomyelitis favored males and the most frequent type was traumatic osteomyelitis,which was mostly caused by open injury and during road accidents.(2)The infection site was frequently located in lower limbs.Monomicrobial infection was the most common infection type,with Staphylococcus aureus as the most frequently detected pathogen.(3)Significant differences were identified regarding sex ratio,median age at diagnosis,side ratio,proportion of multiple infection sites and positive rate of pathogen culture among different types of chronic osteomyelitis(4)Focus debridement and cephalosporins were the mostly used surgical method and intervenous antibiotics,respectively.The surgical efficacy was fine,though different clinical efficacy were found among different therapies.Part Two:Diagnostic Values of Different Serum Inflammatory BiomarkersObjectives:To investigate diagnostic values of preoperative serum levels of WBC,ESR,CRP,PCT,IL-6 and TNF-a for extremity chronic osteomyelitis,differences of serum levels of the biomarkers between/among different gender,age,osteomyelitis type,infection site number,culture outcome,pathogen number and injury feature groups and their influencing factors.Methods:Clinical data were collected in patients who had sought medical attention to the Department of Orthopaedics and Traumatology,Nanfang Hospital between January 2010 and October 2015 with definite diagnosis of extremity chronic osteomyelitis.Data collected included patient ID number,admission number,name,gender,age at diagnosis,type of chronic osteomyelitis,injury and injury feature,multiple or single site infection,culture outcome,polymicrobial or monomicrobial infection,preoperative serum levels of WBC,ESR,CRP,PCT,IL-6 and TNF-α.Statistical analysis:Statistical methods were described in part 1.Additionally,in this section,multiple linear regression analysis was used to investigate potential influencing factors of serum levels of the inflammatory biomarkers.Blom formula was used if dependent variables did not conform to normal distributions.A P value of ≤ 0.05 was defined as statistical difference.Results:A total of 481 patients with 377 males and 104 females were included.Of all the 6 inflammatory markers,IL-6 achieved the highest positive rate(73.14%,128/175),followed by TNF-a(67.06%,112/167),ESR(65.02%,251/386),CRP(54.37%,230/423)and PCT(39.85%,108/271).However,positive rate of WBC was the lowest(21.00%,101/481).Serum inflammatory biomarker with highest positive ratio for traumatic,hematogenous and diabetic foot osteomyelitis was IL-6(75.69%,109/144),ESR(66.13%,41/62)and ESR(95.74%,45/47),respectively.In addition to a significantly higher value of ESR in female patients(P = 0.001),no significant differences were identified regarding other 5 markers between two genders.Patients over 60 years had significantly greater values of WBC(P = 0.000),ESR(P = 0.000),CRP(P = 0.000),PCT(P = 0.000)and TNF-a(P = 0.011)than those below 60 years.Significant differences of serum WBC(P-0.000),ESR(P = 0.000),CRP(P =0.000)and PCT(P = 0.000)were also found among different types of chronic osteomyelitis.Patients with multiple infection sites had statistically higher levels of WBC(P = 0.000),ESR(P = 0.000),CRP(P = 0.000)and PCT(P = 0.000)than those with a single infection site.In addition,patients with positive culture outcomes had significantly higher values of WBC(P = 0.005),PCT(P = 0.044)and TNF-a(P=0.031)than those with negative outcomes.However,among patients with positive culture outcomes,no significant differences were found of the 6 indicators between patients with polymicrobial infections and those with monomicrobial infections.Moreover,no significant differences were found between patients with a medical history of open injury and those with closed injury in addition to a statistically greater WBC level in patients with a medical history of closed injury(P = 0.033).Outcomes of the multiple linear regression analysis revealed that serum WBC level may be associated with gender(P = 0.032)and osteomyelitis type(P = 0.000).ESR level may be associated with age(P = 0.002),osteomyelitis type(P = 0.000)and infection site number(P = 0.049).CRP level may be related to gender(P = 0.006),age(P = 0.012)and osteomyelitis type(P = 0.000).PCT level may be related to gender(P=0.024),osteomyelitis type(P =0·000)and infection site number(P =0.002).IL-6 level may be correlated with osteomyelitis type(P = 0.049)and culture outcome(P = 0.048).However,TNF-a level may be uncorrelated with gender(P =0.372),age(P = 0.055),osteomyelitis type(P = 0.263),infection site number(P =0.752)or culture outcome(P = 0.069).Conclusions:(1)IL-6,TNF-a and ESR were more valuable biomarkers for assisted diagnosis of chronic osteomyelitis.However,diagnostic value of serum WBC is limited.(2)Positive rates of inflammatory markers differred among different types of osteomyelitis.IL-6 achieved highest positive rate in patients with traumatic osteomyelitis,while in patients with hematogenous and diabetic foot osteomyelitis,it was ESR.(3)Serum levels of inflammatory biomarkers may be higher in case of elder patients(≥ 60 years),diabetic foot osteomyelitis,multiple sites of infection and positive culture outcome.(4)Outcomes of the multiple linear regression analysis revealed that chronic osteomyelitis type may be the primary influencing factor of serum levels of the inflammatory biomarkers.Part Three:Association of TNF Family SNPs and Susceptiblility to the Development of Chronic OsteomyelitisObjectives:To investigate associations between TNF family SNPs and the risk of developing chronic osteomyelitis and its subtypes.Methods:This study was designed as a case-control study.Patients were those with definite diagnosis of extremity chronic osteomyelitis,who had sought medical attention to the Department of Orthopaedics and Traumatology,Nanfang Hospital between August 2013 and October 2015.Healthy controls were individuals without any abnormalities after thorough examination in the physical examination center.After signed informed consent,all the participants received collection of 2 ml peripheral blood through elbow vein.Six TNF-a SNPs(rsl 799964,rs1800630,rsl799724,rs1800750,rs1800629 and rs361525)and 1 LTA SNP(rs909253)were genotyped using the SNaPshot method.Statistical analysis:Statistical analysis was performed using the SPSS 13.0 software(SPSS Inc,Chicago,IL,USA).Methods for baseline data comparions between the two groups were described in part two.Chi-square test was used to detect whether genotype distributions of the healthy controls comply with the Hardy-Weinber Equilibrium(HWE).Comparisons for genotype distributions and frequencies of mutant allele between the two groups were conducted using the Chi-square or Fisher exact test.Genetic models were used to evaluate potential association between SNP and risk of developing the disease.Comparisons for genetic models between the two groups were performed using the multiple logistic regression analysis adjusted by gender and age.Significnt difference was defined as P value of ≤ 0.05.Results:A total of 433 participants with 233 patients and 200 healthy controls were included.Similar sex distribution(χ2 = 2.094,P = 0.148)and median age(Z =-0.169,P = 0.866)were identified between the two groups.Outcomes of the LTA polymorphism rs909253 revealed significant difference of genotype distribution between patients CC(30.90%),CT(50.64%),TT(18.45%)and healthy controls CC(17.50%),CT(55.00%)and TT(27.50%)(P = 0.002).The frequency of mutant allele C in patients was significantly higher than that in healthy controls(56.22%vs.45.00%,P = 0.001,OR = 1.570).Outcomes of the 3 genetic models showed significant links between the SNP site and susceptibility to chronic osteomyelitis,including dominant model(CC+CT vs.TT,P = 0.040,OR = 1.615),recessive model(CC vs.CT+TT,P = 0.002,OR = 2.071)and homozygote model(CC vs.TT,P =0.001,OR = 2.532).The above outcomes imply that that the mutant allele C may be a risk factor of chronic osteomyelitis and people with the genotype of CC may be a group of a higher risk to chronic osteomyelitis.Outcome of TNF-a gene polymorphism rs1799964 showed that the frequency of mutant allele T in patient group was significantly higher than that in healthy controls(85.62%vs,80.25%,P =0.035,OR = 1.466).Outcome of recessive model(TT vs.TC+CC,P = 0.048,OR =1.516)indicated significant correlation of this SNP site with the risk of chronic osteomyelitis.The above outcomes imply that the mutant allele T may be a risk factor of chronic osteomyelitis and people with the genotype of TT may be a group of a higher risk to chronic osteomyelitis.Outcomes of the subgroup analysis revealed that in patients with traumatic osteomyelitis,significant difference of LTA gene polymorphism rs909253 was found regarding genotype distribution between patients CC(29.63%),CT(49.21%),TT(21.16%)and healthy controls CC(17.50%),CT(55.00%),TT(27.50%)(P = 0.016).The frequency of mutant allele C in patient group was significantly higher than that in healthy controls(54.23%vs.45.00%,P = 0.010,OR = 1.448).Outcomes of the recessive model(CC vs.CT+TT,P=0.012,OR = 1.868)and homozygote model(CC vs.TT,P = 0.021,OR = 2.016)revealed significant associations between this SNP site and risk of developing traumatic osteomyelitis.The above outcomes imply that that the mutant allele C may be a risk factor of traumatic osteomyelitis and people with the genotype of CC may be a group of a higher susceptibility to traumatic osteomyelitis.In addition,the frequency of mutant allele A of TNF-a gene polymorphism rs1800629 in patients was significantly lower than that in healthy controls(4.23%vs.7.75%,P = 0.040,OR = 0.526).With regard to the outcomes of non-traumatic osteomyelitis(hematogenous and diabetic foot osteomyelitis),significant difference of LTA gene polymorphism rs909253 was found regarding the genotype distribution between patients CC(36.36%),CT(56.82%)and TT(6.82%)and healthy controls CC(17.50%),CT(55.00%)and TT(27.50%)(P = 0.002),The frequency of mutant allele C in patient group was significantly higher than that in healthy controls(64.77%vs.45.00%,P =0.001,OR = 2.247).Outcomes of the dominant model(CC+CT vs.TT,P = 0.008,OR = 5.326),recessive model(CC vs.CT+TT,P = 0.003,OR = 3.123),homozygous model(CC vs.TT,P = 0.001,OR = 9.532)and heterozygous model(CT vs.TT,P =0.030,OR = 4.086)showed significant links between this SNP site and risk of developing non-traumatic osteomyelitis.The above outcomes imply that the mutant allele C may be a risk factor for non-traumatic osteomyelitis and people with the genotype of CC may be a group of a higher risk to non-traumatic osteomyelitis.Additionally,significant differences were also found in TNF-a gene polymorphism rs1800629 by heterozygous model(AG vs.GG,P = 0.029 OR = 2.519),which implies that this SNP may be correlated with the risk of developing non-traumatic osteomyelitis and people with the genotype of CC may be a group of a higher risk to non-traumatic osteomyelitis.Conclusions:(1)Significant associations are found between LTA gene polymorphism rs909253 and the risk of developing chronic osteomyelitis,traumatic and non-traumatic osteomyelitis.The mutant allele C may be a risk factor of chronic osteomyelitis,traumatic and non-traumatic osteomyelitis.People with genotype of CC may be a group of a higher risk to chronic osteomyelitis,traumatic and non-traumatic osteomyelitis.(2)TNF-α gene polymorphism rs1799964 may be associated with the risk of developing chronic osteomyelitis.The mutant allele C of this site may be a risk factor of chronic osteomyelitis.People with the genotype of TT of this site may be a group of a higher risk to chronic osteomyelitis.(3)The mutant allele A of TNF-α gene polymorphism rs1800629 may be a protective factor against traumatic osteomyelitis.Polymorphism of rs1800629 may be associated with the increased risk of developing non-traumatic osteomyelitis and people with genotype of AG of this site may be a group of a higher risk to non-traumatic osteomyelitis.Part Four:Association of IL Family SNPs and Susceptibility to the Development of Chronic OsteomyelitisObjectives:To investigate associations of IL family SNPs and the risk of developing chronic osteomyelitis and its subtypes.Methods:The methods were in consistent with those described in part three.A total of 24 SNPs were genotyped,including IL-1β(rs16944,rs1143627,rs1143634,rs2853550),IL-1α(rs1800587,rs17561),IL-RN(rs4251961,rs419598,rs315951),IL-4(rs2243248,rs2243250),IL-6(rs1800795,rs1800796,rs1800797),IL-8(rs4073,rs2227306,rs2227307),IL-10(rs3024491,rs3024496,rs1800871,rs1800872,rs1800896),IL-17A(rs2275913)and IL-17F(rs763780).Statistical analysis:Statistical analysis methods were described in part 3.Results:A total of 433 participants were included,with 233 patients and 200 healthy controls.Similar sex distribution(χ2 = 2.094,P = 0.148)and median age(Z=-0.169,P = 0.866)were identified between the two groups.Outcome revealed that significant difference was found regarding genotype distribution of IL-1RN gene polymorphism rs4251961 between patients CC(1.29%),CT(12.02%),TT(86.69%)and healthy controls CC(1.50%),CT(21.00%)and TT(77.50%)(P = 0.036).The frequency of mutant allele C in patients was significantly lower than that in healthy controls(7.30%vs.12.00%,P = 0.018,OR = 0.577).Outcomes of the dominant model(CC+CT vs.TT,P = 0.010,OR = 0.512)and heterozygous model(CT vs.TT,P = 0.009,OR = 0.494)revealed significant links between this SNP site and risk of developing chronic osteomyelitis.The above outcomes imply that the mutant allele C of this SNP site may be a protective factor against chronic osteomyelitis.People with CT genotype of this site may be a group with protective effects against chronic osteomyelitis.Significant difference was also found regarding genotype distribution of IL-8 gene polymorphism rs2227306 between patients CC(50.21%),CT(37.34%),TT(12.45%)and healthy controls CC(40.50%),CT(49.00%)and TT(10.50%)(P =0.050).Outcome of the heterozygous model(CT vs.TT,P = 0.024,OR = 0.626)revealed significant link between this SNP site and the risk of chronic osteomyelitis.This result implies that people with CT genotype of this site may be a group with protective effects against chronic osteomyelitis.In addition,results of the dominant model(GG + AG vs.AA,P = 0.026,OR = 1.698)and heterozygous model(AG vs.AA,P = 0.030,OR = 1.733)of IL-1β gene polymorphism rs16944 showed significant associations between this SNP site and the susceptibility to chronic osteomyelitis,implying that people with non-AA genotype may be a group of a higher risk to chronic osteomyelitis.Moreover,outcome of homozygous model(CC vs.GG,P = 0.046,OR = 2.999)of IL-6 gene polymorphism rs1800796 also revealed possible correlation of this SNP site with the risk of chronic osteomyelitis.Outcomes of the subgroup analysis showed that among patients with traumatic osteomyelitis,significant difference of IL-1RN gene polymorphism rs4251961 was found regarding genotype distribution between patients CC(1.59%),CT(10.05%),TT(88.36%)and healthy controls CC(1.50%),CT(21.00%)and TT(77.50%)(P =0.007).The frequency of mutant allele C in patients was significantly lower than that in healthy controls(6.61%vs.12.00%,P = 0.010,OR = 0.519).Outcomes of the dominant model(CC+CT vs.TT,P = 0.005,OR = 0.446)and heterozygous model(CT vs.TT,P = 0.003,OR = 0.409)revealed significant associations of this SNP site with the risk of traumatic osteomyelitis.The above outcomes imply that the mutant allele C may be a protective factor against traumatic osteomyelitis.People with CT genotype of this site may be a group with protective effects against traumatic osteomyelitis.Significant difference was also found regarding genotype distribution of IL-1β gene polymorphism rsl6944 between patients AA(15.87%),CT(51.85%),TT(32.28%)and healthy controls AA(26%),AG(45%),GG(29%)(P = 0.049).Outcomes of the dominant model(GG+AG vs.AA,P = 0.017,OR = 1.854),homozygous model(GG vs.AA,P = 0.041,OR = 1.831)and heterozygous model(AG vs.AA,P = 0.022,OR = 1.869)showed significant link of this SNP site with the risk of traumatic osteomyelitis.The above results imply that people with non-AA genotype of this site may be a group of a higher risk to traumatic osteomyelitis.In addition,statistical differences were identified of IL-1β gene polymorphism rs1143627 between the two groups by dominant model(CT +TT vs.CC,P=0.032,OR = 1.735)and homozygous model(TT vs.CC,P = 0.040,OR = 1.839),implying potential associations between this SNP site with risk of traumatic osteomyelitis.People with genotype of non-CC genotype of this site may be a group of a higher risk of this disease.While in IL-6 gene polymorphism rs1800796,outcomes of the dominant model(CC+CG vs.GG,P = 0.029,OR = 4.184),homozygous model(CC vs.GG,P = 0.026,OR = 4.378)and heterozygous model(CT vs.CC,P = 0.046,OR=3.834)revealed significant links of this SNP site with susceptibility to traumatic osteomyelitis.The outcomes imply that non-GG genotype of this site may be a group of a higher risk of developing traumatic osteomyelitis.Among patients with non-traumatic osteomyelitis,significant difference of IL-17F gene polymorphism rs763780 was found regarding the genotype distribution between patients CC(2.27%),CT(47.73%)and TT(50.00%)and healthy controls CC(1.00%),CT(26.50%)and TT(72.50%)(P = 0.013).The frequency of mutant allele C in patient group was significantly higher than that in healthy controls(26.14%vs.14.25%,P = 0.006,OR = 2.129).Outcomes of the dominant model(CC+CT vs.TT,P=0.007,OR = 2.560)and heterozygous model(CT vs.TT,P=0.008,OR = 2.537)showed significant associations between the SNP site and risk of developing non-traumatic osteomyelitis.The above results imply that the mutant allele C may a risk factor of non-traumatic osteomyelitis.People with CT genotype of this site may be a group of a higher risk to non-traumatic osteomyelitis.In addition,statistical difference of IL-1RN gene polymorphism rs419598 was found regarding the genotype distribution between patient group CC(2.27%),CT(2.27%)and TT(95.45%)and control group CC(0%),CT(11.50%)and TT(88.50%)(P =0.024).Conclusions:(1)Significant link is found between IL-1RN gene polymorphism rs4251961 and the risk of developing chronic and traumatic osteomyelitis.The mutant allele C may be a protective factor against chronic and traumatic osteomyelitis.People with CT genotype of this site may a group with protective effects against chronic and traumatic osteomyelitis(2)Significant association is identified between IL-1β gene polymorphism rs16944 and the risk of developing chronic osteomyelitis,especially for traumatic osteomyelitis.People with non-AA genotype of this site may be a group of a higher risk to develop traumatic osteomyelitis.(3)Significant correlation is observed between IL-1β gene polymorphism rs1143627 and susceptibility to the development of traumatic osteomyelitis.People with non-CC genotype of this site may be a group of a higher risk to develop traumatic osteomyelitis.(4)Significant association is found between IL-6 gene polymorphism rs1800796 and the risk of developing chronic osteomyelitis,especially for traumatic osteomyelitis.People with non-GG genotype of this site may be a group of a higher risk of developing traumatic osteomyelitis.(5)Significant link is identified between IL-8 gene polymorphism rs2227306 and susceptibility to chronic osteomyelitis.People with CT genotype of this site may be a group with protective effects against chronic osteomyelitis.(6)Significant correlation is observed between IL-17F gene polymorphism rs763780 and the risk of developing non-traumatic osteomyelitis.The mutant allele C may be a risk factor of non-traumatic osteomyelitis.People with CT genotype of this site may a group with a higher risk to develop non-traumatic osteomyelitis.
Keywords/Search Tags:Chronic osteomyelitis, Clinical characteristics, Serum inflammatory markers, Single Nuclotide Polymorphism, Pathogenesis
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