| Periodontal diseases are one of the two most common oral diseases and the major cause of tooth loss in adults. In China the incidence of periodontal disease is higher than that of caries. Periodontal diseases mainly consist of gingivitis and peirodontitis. Chronic periodontitis (CP), as a kind of chronic inflammatory disease, is one type of the most commonly seen periodontitis. The main clinical manifestations of CP include gingival inflammation, periodontal attachment loss, alveolar bone absorption, tooth mobilization and dislocation, and even tooth loss in the end. Although periodontal bacteria are the causative agents in periodontitis, bacteria alone cannot cause the disease. The host susceptibility is also a fundamental factor. Studies in recent years show host susceptibility that associated with heredity can effect and alter host response to bacteria and determine the subsequent progression and severity of the disease.As the study of biological effect of cytokine (CK) goes further, studies about the relationship between cytokine gene polymorphism and diseases show gene variation regulating cytokines can explain the difference among individuals during disease progression. Previous studies about cytokines related to periodontitis are mainly focused on interleukin-1 (IL-1), tumor necrosis factor a (TNF-a), IgG2 Fc fragment receptor gene and vitamin D receptor (VDR). IL-1 gene polymorphism is the first reported interleukin genetic marker associated with periodontal diseases. Interleukin-4 (IL-4) is a pleiotropic cytokine that inhibits Thl cells while stimulating a Th2-type of immune response. It is also a potent downregulator of macrophage function and induces apoptosis in monocytes. IL-4 inhibits the persistence of macrophages in periodontitis lesions and downregulates CD 14 receptor, one of the key receptors for lipopolysaccharides. Thus, it was proposed that a lack of downregulation of monocytes by IL-4 leads to tissue destruction in periodontitis. Several polymorphisms in the IL-4 gene include a single nucleotide polymorphism (SNP) C to T in the IL-4 promoter region at position -590, one SNP at -34 C/T, and a 70bp variable number tandem repeat (VNTR) in the third intron, some of them are implicated in the regulation of IL-4 production. The correlation between IL-4 gene polymorphism and the risk for periodontitis was reported in others countries, while the findings in these studies are contradictory. There is no report on the characteristic of IL-4 gene polymorphism in Chinese chronic periodontitis patients. Hence, the aim of this study is to investigate the correlation between SNP in IL-4 promoter region at position -590 and -34 and the susceptibility to chronic periodontitis in Chinese Han nationality people..Objective:The aim of this study is to investigate the correlation of the IL-4 polymorphisms in the promoter region (-590 C to T and -34 C to T) and the susceptibility to chronic periodontitis in Chinese Han nationality people.Methods:All subjects were recruited from outpatients and inpatients referred to Guangdong Provincial Stomatological Hospital. All patients were 40 years 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 preceding 3 months, receiving periodontal therapy in the preceding 1 year, and pregnant or lactating females.The subjects were categorized into two groups:the chronic periodontitis group (n=104) and healthy control group (n=106). CP patients were identified based on the clinical criteria proposed by the 1999 International World Workshop for a Classification of Periodontal Disease and Conditions. The following data of the subjects were recorded:gender, age, ethnicity, smoking status, body weight, height, medical history and periodontal history. Clinical periodontal parameters of the six index teeth (11,16,26,31,36, and 46) 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 than 3mm, no attachment loss, gingival recession less than lmm, no sites with bleed on probing (BOP), and a general healthy condition. The status of gender, age, nationality, smoking, body weight, body height, stress, medical history, and periodontal history of each participant were recorded. 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-100 method. The DNA concentration was estimated by using a spectrophotometer. Genotyping of the -590 and -34 in IL-4 promoter 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 SPSS 10.0 was used to detect significant differences between the study groups.x±s was used to describe quantitative data, while t-test or analysis of variance (ANOVA) was used to analyze quantitative data. Chi-Square (χ2) 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 than 0.05 was considered statistically significant.Results:Age 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 (χ2=1.904, P=0.386) was found in genotype distribution (CC, CT, and TT) of IL-4 -590 between CP group and control group. No significant difference (χ2=0.771, P=0.380) was found in allele frequencies of IL-4-590 between CP group and control group. No significant difference (χ2=2.081, .P=0.353) was found in genotype distribution (CC, CT, and TT) of IL-4 -34 between CP group and control group. No significant difference (χ2=1.995,P=0.158) was found in allele frequencies of IL-4 -34 between CP group and control group.Two variables, age and number of missing teeth, were significantly different between the CP and control groups (P=0.012; P=0.002) 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-4 -590 gene polymorphism (p=-0.279, W=1.116, P>0.05, OR=0.756) and IL-4 -34 gene polymorphism (β=0.423, W=2.425, P>0.05, OR=1.527) were not influential factors of CP. While the number of missing teeth was a influential factor of CP (β=-0.183, W=5.047, P<0.05, OR=0.833).The allele frequency of T in IL-4-590 were 80% in population of our study, which was close to Japanese and China Taiwanese but obviously higher than Caucasian (16.2%～47.6%).The results of direct DNA sequencing were the same with the results of PCR-RFLP.Conclusion:1. IL-4-590 C/T gene polymorphism is not a susceptible factor of chronic periodontitis in Chinese Han nationality population.2. IL-4-34 C/T gene polymorphism is not a susceptible factor of chronic periodontitis in Chinese Han nationality population.3. In terms of single nucleotide polymorphism in IL-4 promotor, Chinese Han nationality population has a different gene background compared with Caucasian, while has a similar gene background compared with east Asian population such as Japanese and Korean. |
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