| Lumbar disc herniation frequently occurs in the clinic,especially in patients between 20 and 50 years of age,and the most common symptom is lumbocrural pain.Patients can also experience a numb or tingling feeling in one or both legs.The pathogenesis of lumbar disc herniation is very complex and to date the most accepted causes for development of lumbar disc disease are physiological aging and ‘‘degeneration,'' intervertebral disc injury,or spinal overload.However,tobacco smoke and others arealso risk factors for developing lumbar disc disease,and many recent studies showed that genetic factors also play an important role in the development of intervertebral disc disease.Lumbar disc herniation seriously affects the patient's ability to work and the quality of life because of long duration,delay no more,easy to break out repeatedly.It has brought the social burden of economy and spirit and become a major public health problem of the whole society.It has been increasingly recognized that lumbar disc pain may be pathophy-siologically induced by chemical inflammation although the inflammatory factors that contribute to lumbar disc herniation and pain remain to be determined.With the rapid development of molecular biology and molecular immunology for studying cytokines and chemokines,increasing research attention has been given to understanding the pathogen-nesis of intervertebral disc degeneration.Indeed,various cytokines participate in the pathophysiological process of disc degeneration.In particular,interleukin 6(IL-6)and IL-10 were shown to be highly expressed and activated in herniated disc and surrounding tissues,which presented as important pro-and anti-inflammatory cytokines,respectively,in the human body.A paired casecontrol study was conducted to investigate the genetic susceptibility gene of lumbar disc herniation,analyze the environmental risk factors of suffering from lumbar disc herniation disease and explore environmental risk factors and their interactions in lumbar disc herniation.provide information for clinical prewention and treatment of lumbar disc herniation new ideas.Objective: To investigate the association of single-nucleotide polymorphisms(SNPs)in pro-inflammatory cytokines interleukin 6(IL-6)and 10 with risk of lumbar disc herniation,analyze the environmental risk factors of suffering from lumbar disc herniation disease,explore the etiologic of inflammatory genes?environmental risk factors and their interactions in lumbar disc herniation,provide information for the study of etiology?prevention and reproductive health service of lumbar disc herniation.Methods: 1.A paired casecontrol study was conducted including 267 patients with lumbar disc herniation and 300 controls with a ratio of To investigate cases and controls by questionnaire.The self-designed questionnaire was used to collect the information on geographic charaeterestus,occupation,lifestyle,biological factors and psychological faetors.2.Peripheral venous blood samples were collected and DNA was extracted from leukocytes.Taq Man technology was used to detect the SNPs of genes-572C/G and-174G/C of IL-6 promoter and genes-592A/C and-1082G/A of IL-10 promoter.We analyzed the association and differences in gene polymorphisms of IL-6 and IL-10 between lumbar disc herniation group and non-lumbar disc herniation group.3.The correlations between the risk of lumbar disc herniation and inflammatory genes?environmental risk factors and their interactions were evaluated by non-conditional Logistic regression models.4.All statistics were analyzed by SPSS13.0 soft package?haploview4.1(http://www.broad.mit.edu/mpg/haploview/)and SNPstats(AVailability:http://bioinfo.iconcologia.net/ SNPstats).Results: 1.Significant differences was observed in IL-6-572C/G genotype between lumbar disc herniation group(CC51.69%,CG42.32%,GG5.99%)and the control group(CC64.33%,CG24.0%,GG1.67%)(P<0.05).Relative risk test of genotype frequency showed that the risk of G allele carriers suffering from lumbar disc herniation was 1.69 times as high as that of the CC genotype(95% CI: 1.16–2.39,P < 0.01).2.There was no significant diference in distribution of the IL-6 gene-174 site genotype and allele frequency between two groups(P>0.05).3.There was no significant diference in distribution of the IL-10 gene-592 site genotype and allele frequency between two groups(P>0.05).4.Significant differences was observed in IL-10-1082A/G genotype between lumbar disc herniation group(AG26.22%,AA73.78%)and the control group(AG11.67%,AA88.33%)(P<0.05).Relative risk test of genotype frequency showed that the risk of G allele carriers suffering from lumbar disc herniation was 2.69 times as high as that of the AA genotype(95% CI: 1.42-6.33,P<0.05).5.There was no significant diference in age,SI,drinking,humid residence between two groups(P>0.05).Hoewever,the two groups differed significantly(P<0.05)in body mass index,education background,job category,lumbar vertebral loads,commonly used working posture,time of univalent work,diet preference,bed type,spare-time exercises.histoyr of lumbar injury,the family history of lumbar disc herniation,disposition.The results of multivariate logistic regression analysis showed that body mass index(OR=2.975),lumbar vertebral loads(OR=3.293),commonly used working posture(OR=1.245),histoyr of lumbar injury(OR=1.422),the family history of lumbar disc herniation(OR=3.872)were associated with lumbar disc herniation.6.The gene-environment interaction analysis revealed that super-multiplicative interactions respectively between IL-6-572 G allele frequency and lumbar vertebral loads(serious),and sub-multiplicative interactions respectively between IL-10-1082 G allele frequency and lumbar vertebral loads(serious),IL-10-1082 G allele frequency and commonly used working posture(repetitive bending).Conclusion:1.A correlation was found between IL-6-572C/G polymorphism and lumbar disc herniation,and the G allele may be the genetic susceptibility gene causing lumbar disc herniation.2.The mutation rate of the IL-6 gene-174 site was very low,and there was no significant correlation between its polymorphism and lumbar disc herniation.3.No significant correlation was found between the polymorphism of IL-10 gene promoter-592 site and the onset of lumbar disc herniation.4.A correlation existed between the polymorphism of IL-10-1082A/G and the lumbar disc herniation,and the G allele may be the genetic susceptibility gene that caused the lumbar disc herniation.5.Body mass index,lumbar vertebral loads,commonly used working posture,histoyr of lumbar injury,the family history of lumbar disc herniation were risk factors of lumbar disc herniation in a northen Chinese Han population.6.IL-6-572C/G?IL-10-1082A/G genes and lumbar vertebral loads and their interactions play important roles in the pathogenesis of lumbar disc herniation;IL-10-1082A/G genes and commonly used working posture and their interactions play important roles in the pathogenesis of lumbar disc herniation.It suggests that the risk of lumbar disc herniation may be codetermined by environmental factors and inherited susceptibility genes,and that the mechanisms of interactions vary in different genotypes and the same or different environmental factors;relieving lumbar vertebral loads and adjusting commonly used working posture can reduce the lumbar disc herniation's risk of popele with IL-6-572C/G gene G allele and IL-10-1082A/G gene G allele. |
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