The Association Of Interleukin-13Gene Polymorphisms With Chronic Periodontitis

Background:Periodontitis is a chronic and infectious disease. It is one of two most common oral diseases with comparably higher incidence rate in the world, and caused by oral bacteria, resulting in irreparable periodontal attachment loss, alveolar bone destruction, and eventually leading to tooth loss. The periodontitis is initiated but not solely caused by the dental plaque biofilm bacteria and their products. As shown by more and more evidences, the gene polymorphism of some specific chromosomes could affect the incidence of periodontitis, and determine the subsequent progression and severity of the disease.Gene variation regulating cytokines can explain the difference among individuals during disease progression. In recent years, some researches with significant results have been reported on the correlation of periodontitis with some cytokines such as interleukin-1(IL-1). interleukin-6(IL-6), tumor necrosis factor-α (TNF-α), and vitamin D receptor (VDR). But there has not yet any report concerning researches on its association with the gene polymorphism of interleukin-13.In the destruction of periodontal disease, Th2cells cytokines such as IL-4and IL-13favorite the B-cells mediated humoral immunity and improve the symptom of inflammatory diseases. IL-13has the anti-inflammatory effect and inhibits the secretion of tumor necrosis factor-a (TNF-a) of circulating monocyte after released by Th2cells. IL-13induces fibrosis via promoting and activating the release of transforming growth factor-β1(TGF-β1). IL-13also inhibits osteoclast differentiation and bone resorption via the OPG system. IL-13and IL-4are30%homogenous in amino acid sequence, and act through their own receptor (i.e. IL-13R and IL-4R sharing IL-4Ra chain). Therefore, IL-13and IL-4overlap in the biological role to some extent, and are the sole cytokines to directly promote IgE synthesis in human body. As shown by some researches, IgE significantly increased in the gingival tissues of chronic periodontitis patients, and IL-13and IL-4at the periodontal foci could stimulate B cells in producing IgE and IgG to antagonize the lipopolysaccharide (LPS) of periodontal pathogens. As verified by foreign researches, the single-nucleotide polymorphisms(SNPs) in the IL-4promoter region at position-590and70bp variable number tandem repeat(VNTR) in the second intron are associated with aggressive periodontitis of Caucasia population. As also shown by domestic researches, the single-nucleotide polymorphisms(SNPs) in the IL-4promoter region at position-590was susceptible to chronic periodontitis of Chinese Han population, which was one of genetic factors for chronic periodontitis among Han population. Recent study states that IL-4was related to periodontitis, and the gene variation of IL-13was related to asthma, systemic sclerosis and rheumatoid arthritis. Moreover, IL-13and IL-4are similar in the biological role. Therefore, the single-nucleotide polymorphisms in the IL-13-1112and IL-13+1923is preliminarily assumed to play a certain role in the progress of chronic periodontitis.Objective:The aim of this study is to investigate the correlation of the IL-13-1112C/T promoter polymorphism and IL-13+1923C/T intron polymorphism and the susceptibility to chronic peridontitis(CP) in Chinese Han nationality people.Methods:All subjects were recruited from outpatients and inpatients referred to Guangdong Provincial Stomatological Hospital. All Patients were40years old or greater, Chinese Han descent and genetically unrelated. Exclusion criteria were as follows:known systemic disease, history of orthodontic treatment, receiving systemic antibiotic treatment in the preceding3months, receiving periodontal therapy in the preceding1year, and pregnant or lactating females. The subjects were categorized into two groups:the chronic periodontitis group(n=110) and healthy control group(n=106).CP patients were identified based on the clinical criteria proposed by the1999International World Workshop for a Classification of Periodontal Disease and Conditions. The following data of the subjects were recorded:name, gender, age, ethnicity, smoking status, body weight, height, mental stress, medical history and periodontal history. Clinical periodontal parameters of the six index teeth(11,16.26,31.36,and46)were obtained at six sites for each examined tooth. Moreover, missing teeth were recorded except for the third molars. The criteria of healthy controls included probing pocket depth(PD) less than3mm, no attachment loss, gingival recession less than1mm.no sites with bleed on probing(BOP),and a general healthy condition. A buccal swab sample was obtained by twisting a swab inside each participant’s cheek. In order to keep accuracy and consistency, all periodontal examinations were carried out by a single trained and calibrated examiner.Genomic DNA was extracted from buccal swabs by CHELEX-100method. The DNA concentration was estimated by using a spectrophotometer. Genotyping of the-1112in IL-13promoter and+1923in IL-13intron was performed with polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP) technique. To confirm the accuracy of the PCR-RFLP,20%samples were randomly selected for direct DNA sequencing.A computer package SPSS16.0was used to detect significant differences between the study groups. x±S was used to describe quantitative data, while t-test or Mann-Whitney test was used to analyze quantitative data. Chi-Square(x2) test was used to investigate genotype distribution and allele frequencies in each locus between the study groups. Logistic regression analysis was used to perform multifactor analysis.P value less than0.05was considered statistically significant.Results:Smoking status and number of missing teeth showed a significant difference(P <0.05) when clinical parameters of CP and control group were compared. No significant difference(x2=2.015, P>0.05) was found in genotype distribution(CC,CT,and TT) of IL-13-1112between CP group and control group. No significant difference(x2=0.886, P>0.05) was found in allele frequencies of IL-4-1112between CP group and control group. No significant different(x2=1.006, P>0.05) was found in genotype distribution(CC,CT,and TT) of IL-13+1923between CP group and control group. No significant difference(x2=0.038,P>0.05) was found in allele frequencies of IL-13+1923between CP group and control group.Three variables, smoking status, stress and number of missing teeth, w;ere significantly different between the CP and control groups(P=0.049,P=0.001,P=0.000) when clinical parameters comparison was performed, so the logistic regression analysis was regulated for age and number of missing teeth. It was found both IL-13-1112gene polymorphism(β=-0.250, W=0.890, P>0.05) and IL-13+1923gene polymorphism(β=0.020, W=0.009, P>0.05) were not influential factors of CP. While the number of missing teeth(p=0.328, W=12.237, P=0.000) were a influential factor of CP.Conclusion:1. IL-13-1112C/T gene polymorphism is not a susceptible factor of chronic periodontitis in Chinese Han nationality population.2. IL-13+1923C/T gene polymorphism is not a susceptible factor of chronic periodontitis in Chinese Han nationality population.3. The main genotype of IL-13-1112is CC genotype and the main allele of IL-13-1112is C allele. The main genotype of IL-13+1923is TT genotype and the main allele of IL-13+1923is T allele.