IL-1β-511基因多态性与牙周炎合并2型糖尿病的关联研究

目的:研究白细胞介素-1单核苷酸多态性与牙周炎合并2型糖尿病患者牙周炎易感性的关系.方法:从解放军第306医院口腔中心和糖尿病中心分别选取120例单纯2型糖尿病患者(对照组)和110例牙周炎合并2型糖尿病患者(实验组)作为调查对象.经均衡性检验两组在年龄、性别、全身病史、牙周病史、病程、吸烟史等无显著性差异后,提取外周血基因组DNA,采用聚合酶链式反应—限制性片段长度多态性方法对白细胞介素IL-1β-511基因位点进行基因型分析.结果:基因多态性分析显示:实验组IL-1β-511 A等位基因的频率较对照组明显增高,差异具有统计学意义(OR=1.6930,95％CI为1.1359 to 2.3487,P＜0.05).结论:IL-1β-511 A与糖尿病患者牙周炎的发生有密切关系.     

IL-1A＋4845-Fnu4HⅠ基因多态性与慢性牙周炎易感性关系的研究

目的: 探讨中国汉族人IL-1A 4845-Fnu4H I基因多态性与慢性牙周炎易感性的关系.方法:收集66例中重度慢性牙周炎(CP)病人,50例健康对照者的静脉血,提取外周静脉血白细胞DNA,采用PCR-RFLP方法,检测IL-1A 4845-Fnu4H I基因型,比较两组受试者等位基因型检出率的差别.结果:CP组IL-1A 4845-Fnu4H I等位基因2的检出率和健康对照组无显著性筹异(OR=1.05;95%CI=0.38～2.84:P＞0.05).结论:IL-1A 4845-Fnu4H I等位基因2可能与汉族中重度慢性牙周炎遗传易感性无关.     

新疆不同民族慢性牙周炎白IL-1基因多态性的研究

目的：探讨新疆哈萨克族、维吾尔族与汉族慢性牙周炎患者白细胞介素-1（Interleukin-1，IL-1）基因多态性。方法：取患者双侧颊黏膜拭子，采用Chelex-100法提取DNA，采用序列特异引物聚合酶链反应法（PCR）和聚合酶链反应-限制性片段长度多态性（PCR—RFLP）法对47例新疆哈萨克族慢性牙周炎患者IL-1B＋3953／TaqⅠ和IL-1B-511／AvaⅠ位点基因型进行检测，并与维吾尔族、汉族慢性牙周炎患者进行比较，分析各组基因型分布的差异。结果：IL-1B＋3953／TaqⅠ和IL-1B-511／AvaⅠ基因型分布在新疆哈萨克族与汉族、维吾尔族与汉族之间差异有统计学意义（p〈0．05）。结论：IL-1B＋3953／TaqⅠ和IL-1B-511／AvaⅠ位点基因多态性在慢性牙周炎患者中存在种族差异。     

基因位点单核苷酸多态性与牙周炎易感性的关系

单核苷酸多态性(SNP)作为一种研究基因位点突变与疾病易感性和相关性的新方法,已经在很多领域开展。牙周炎是一种宿主易感性的疾病,本文就某些基因位点SNP与牙周炎易感性的相关性研究作一综述。     

IL-1β和TNF-α基因多态性与慢性牙周炎的相关性分析

目的探讨细胞因子基因多态性与中、重度慢性牙周炎遗传易感性的关系。方法采用PCR-RFLP方法检测IL-1B 3953和TNF-Α-308基因型。采用多变量Logistic回归模型,确定IL-1B 3953和TNF-Α-308等位基因2阳性基因型对中、重度慢性牙周炎的影响。结果中、重度慢性牙周炎组IL-1B 3953(28.23%)和TNF-Α-308(29.03%)等位基因2阳性基因型出现的频率和对照组(分别为13.95%和11.05%)相比有显著性差异(P<0.01)。多变量Logistic回归模型分析结果显示,携带等位基因2阳性基因型的个体较携带阴性型个体发生中、重度慢性牙周炎的危险性相对较大,且统计学有显著意义(IL-1B 3953和TNF-Α-308分别为P<0.05,P<0.01)。结论IL-1B 3953和TNF-Α-308等位基因2阳性基因型可能与中、重度慢性牙周炎易感性有关。     

白细胞介素-1基因多态性与侵袭性牙周炎的关系

目的：研究中国人群中白细胞介素-1（IL-1）基因多态性与侵袭性牙周炎（AgP）之间的关系。方法：提取122例AgP患者和95例健康对照者外周静脉血基因组DNA,采用聚合酶链反应（PCR）分析IL-1A＋4845、IL-1B＋3954位点的单核苷酸多态性（SNP）及IL-1RN第二内含子中的可变数目重复序列（VNTR）多态性,采用多因素Logistic回归模型,进行两组之间基因型、等位基因分布差异的比较。结果：在IL-1A＋4845位点,AgP组男性患者A2^＋基因型的频率较男性健康组显著升高（P〈0．05=0．039）,等位基因A2的携带率也显著升高（P〈0．05=0．049）;未发现IL-1B＋3954位点和IL-1RN VNTR的多态性与AgP关联;未发现IL-1各复合基因型与AgP存在明显关联性。结论：IL-1A＋4845位点的SNP可能与中国人群中男性个体的AgP易感性有关。     

白细胞介素-1单核苷酸多态性与甘肃回族、东乡族人群慢性牙周炎的相关性研究

目的 通过检测并分析白细胞介素(IL)-1B+3954位点的单核苷酸多态性(SNP),探索其与甘肃回族与东乡族人群慢性牙周炎的关系.方法 收集215例回族、东乡族慢性牙周炎患者及219例正常对照组健康者的静脉血,提取外周静脉血白细胞DNA,采用聚合酶链式反应-限制性片段长度多态性技术(PCR-RFLP)方法检测IL-1...     

IL-6-572基因多态性与侵袭性牙周炎易感性的相关性研究

目的 研究白细胞介素-6(interleukin-6,IL-6)-572位点基因多态性与侵袭性牙周炎易感性的关系.方法 采用病例对照试验设计,从广东汉族人群中选择83例侵袭性牙周炎(aggressive periodontitis,AgP)患者(AgP组)及79例牙周健康者(对照组),采用聚合酶链反应—限制性内切酶片段长度多态性分析方法对IL-6-572位点基因多态性进行检测,分析组间基因型频率及等位基因分布的差异.结果 IL-6基因启动子区-572位点G/C基因型在AgP组、对照组中的分布频率差异有统计学意义(x2=13.710,P=0.001).AgP组与对照组相比,G、C等位基因频率分布差异有统计学意义(x2=13.213,P<0.001),G等位基因相对于C等位基因:OR值为2.988,95%CI:1.634~5.465.结论 IL-6-572 G/C位点的基因多态性同中国广东汉族人群侵袭性牙周炎患病易感性可能存在相关关系,IL-6-572 G等位基因可能是广东汉族人群AgP遗传易感性的高风险因素.     

白细胞介素-1B-511基因多态性与牙周炎进展的关系

目的 了解不同程度慢性牙周炎病程的自然发展及其与白细胞介素-1B-511（IL-1B-511）基因多态性的关系。方法 选取慢性牙周炎患者100例,分别在基线、6个月、12个月时检查全口余留牙的临床附着丧失量（AL）,每个牙检查6个位点。棉拭子刮取患者颊黏膜脱落细胞,采用聚合酶链反应检测IL-1B-511基因型分布。结果 1年内,100例患者平均AL增加1.43 mm;病情进展缓慢（全口年平均AL增加不超过1.0 mm）的16例,进展快速（全口年平均AL增加超过1.0 mm）的84例;IL-1B-511基因型分布及等位基因分布频率在病情进展缓慢和快速的患者间未发现统计学差异（P>0.05）。基线检查时为轻中度牙周炎的患者在1年的观察期内出现全口年平均AL增加超过1.0 mm的人数多于重度牙周炎患者（P<0.05）;从患牙部位看,两次复查时AL增加均超过2.0 mm的牙位以磨牙为多,多于前牙和前磨牙;且在重度牙周炎患者中更易出现,多于轻中度牙周炎患者（P<0.05）。结论 不同个体牙周炎的进展程度不一致;AL改变与白细胞介素-1基因多态性尚未发现有相关性。     

2型糖尿病合并牙周炎患者血清白细胞介素-1水平的检测

目的探讨2型糖尿病合并牙周炎患者血清白细胞介素-1（interleukin-1,IL-1）蛋白水平的表达。方法选择健康对照、糖尿病、重度慢性牙周炎和重度慢性牙周炎伴2型糖尿病患者各32例。用酶联免疫ELISA法测定血清IL-1α、IL-1β水平。结果 2型糖尿病合并牙周炎患者的血清IL-1β含量明显高于不伴牙周炎的糖尿病患者（P〈0.05）,牙周炎组高于健康对照组。4组中IL-1α水平无显著差异。结论 2型糖尿病合并牙周炎患者血清IL-1β水平明显升高。     

Association of CXCL12 gene promoter methylation with periodontitis in patients with diabetes mellitus type 2

ObjectivesCXCL12 is widely expressed, constitutive chemokine involved in tissue repair and regeneration, while the extent of its expression is important in various chronic inflammatory conditions. Involvement of DNA methylation in CXCL12 gene suppression (CXCL12) has been shown in malignancy and some autoimmune diseases. The aim of this study was to investigate whether the alterations in DNA methylation of CXCL12 are also involved in progression of periodontitis in combination with diabetes, as these chronic inflammatory conditions are strongly interrelated.DesignStudy included 72 subjects divided in three groups: healthy control (C, n = 21), periodontitis (P, n = 29) and diabetes/periodontitis group (D/P, n = 22). DNA extracted from epithelial cells obtained by sterile cotton swabs from buccal mucosa was subjected to methylation specific polymerase chain reaction (MSP) to obtain DNA methylation pattern of CXCL12 promoter.ResultsCXCL12 promoter was predominantly unmethylated in all groups. However, increase in the frequency of the methylated form and increase in percent of methylation of CXCL12 promoter in periodontitis and diabetes/periodontitis group compared to control group were found, although without statistical significance. However, statistically significant increase in Tm of MSP products in diabetes/periodontitis group was observed. Correlation analysis revealed statistically significant relationship between the extent of DNA methylation of the CXCL12 promoter and periodontal parameters, as well as between DNA methylation of CXCL12 and glycosylated hemoglobin.ConclusionPresented results suggest that chronic inflammation contributes to the change of CXCL12 DNA methylation in buccal cells and that DNA methylation profile of CXCL12 promoter plays important role in development and progression of periodontal disease.     

RAGE基因多态性与2型糖尿病伴慢性牙周炎遗传易感性的相关研究

［摘要］ 目的 探讨晚期糖基化终产物受体(receptor for advanced glycation end products, RAGE)基因的5个SNP位点在2型糖尿病伴慢性牙周炎、单纯慢性牙周炎、健康对照北方汉族人群中分布的差异,从而研究RAGE基因是否为糖尿病和牙周炎可能的致病易感基因。方法 运用飞行时间质谱法检测19例2型糖尿病伴慢性牙周炎患者(DM组),22例单纯慢性牙周炎组(CP组)以及54例健康对照组(H组)全血基因组DNA中5个单核苷酸多态性(single nucleotide polymorphism, SNP)位点。结果 rs17846808、rs1800625、rs184003、rs2070600、rs3134940基因多态性在三组间分布无差异。DM组中的rs3134940 A/A（野生纯合子）基因型人群的龈沟出血指数(sulcus bleeding index,SBI)显著高于(A/G+G/G,杂合子和突变纯合子)基因型人群的SBI。CP组中的rs1800625 (T/C+C/C)和rs3134940 (A/G+G/G,杂合子和突变纯合子)基因型人群缺失牙数显著性增高。结论 RAGE基因并非2型糖尿病以及慢性牙周炎的易感基因。rs3134940 G等位基因可能在2型糖尿病伴慢性牙周炎进展过程中起到一定保护作用。     

Association of interleukin-1 polymorphisms with aggressive periodontitis

BACKGROUND: Genetic polymorphisms for interleukin (IL)-1alpha and -1beta have been proposed as potential genetic markers for periodontal diseases. Since the prevalence of these polymorphisms could be race-related, and no data exist about the frequency of these polymorphisms in the Chilean population, the aim of the current study was to investigate the association of the interleukin-1 gene polymorphisms with aggressive periodontitis (AgP). METHODS: Thirty-six patients with AgP, 75 healthy controls, and 75 subjects of unknown periodontal status (reference population) were genotyped for the IL-1A -889 and IL-1B +3954 loci, by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion and gel electrophoresis. Data were analyzed using the chi-square test, calculating odds ratios (OR) and confidence intervals (CI). RESULTS: The prevalence of the positive composite IL-1 genotype was higher in patients (25%) than in healthy controls (12%), but the difference was not significant (P= 0.14). The IL-1B +3954 homozygous for allele 1 frequency was higher in controls than in patients suggesting a protective factor for AgP. The heterozygous for allele 2 of the IL- 1B showed a significant association with AgP (OR = 2.86, 95% CI 1.06 to 7.71, P= 0.030). No association was observed in localized AgP and generalized AgP between the extent of disease and the presence of the composite positive genotype. Because the number of smokers was too small in patients and in controls, no other analyses were performed. CONCLUSION: The results of the present study support a positive association between AgP and the presence of the IL-1B +3954 allele 2 polymorphism.     

2型糖尿病患者慢性牙周炎细菌学研究

目的 :研究 2型糖尿病患者慢性牙周炎的龈下菌群以及菌群变化与血糖、糖化血红蛋白的关系。方法 :细菌学厌氧培养、PCR检测技术。结果 :2型糖尿病患者慢性牙周炎的龈下菌群以厌氧菌为主。产黑菌、二氧化碳噬纤维菌数量与糖尿病患者空腹血糖、糖化血红蛋白之间存在正相关关系。产黑菌、二氧化碳噬纤维菌数量随患者空腹血糖、糖化血红蛋白的升高而增加。结论 :2型糖尿病慢性牙周炎患者龈下菌斑相关菌与血糖、糖化血红蛋白变化密切相关     

糖尿病与牙周炎的相互关系

探讨牙周炎与糖尿病之间的双向关系。一些研究表明，糖尿病的表征可以表现为牙周炎，同时也可能成为糖尿病的危险因素，两者相互影响，互为因果。本文就两者相互作用的病理基础、临床表现及治疗特点进行综述，以期对今后的治疗有所裨益。     

Association of interleukin-1 polymorphisms with periodontitis in Down syndrome

This study examined the association of IL1 genetic polymorphisms (IL-1A +4845, IL-1B +3954 & IL-1RN +2018) with periodontal disease status of Down syndrome (DS) individuals. Fifty-four DS patients (18-56 yr, 48.15% male, 77.78% Caucasians) were recruited from the Georgia Regional Hospital (GRH) health care system. Two comparable groups (71 mentally retarded patients and 87 control subjects) were also recruited. All subjects were nonsmokers. Periodontal evaluations (plaque index, gingival index, bleeding-on probing and clinical attachment levels (AL)), personal and professional dental care habits were recorded. Blood was collected by a venipuncture. The IL-1A +4845, IL-1B +3954 & IL-1RN +2018 loci were genotyped by the TaqMan assay. No statistically significant differences were noted in the distribution of IL-1 gene polymorphisms between the three groups. The IL-1 variant genotypes varied by race; for both IL-1A and IL-1RN, the variant gene was significantly more prevalent among whites than non-whites (ps > 0.1). ANCOVA, which also adjusted for age, showed a 3-way interaction among dental visits, gene variation and Down status [(F(1, 179) = 3.96, P = 0.048 in White subjects and F(1, 241) = 2.96, P = 0.087 in all subjects). Post-hoc t-tests confirmed lower levels of AL in IL-1RN-variant Down subjects receiving more frequent dental visits (P < 0.05). ANCOVA, which also adjusted for age, showed an interaction between IL-1A/B gene variation and Down status (F(1, 174) = 3.04, P = 0.083 in White subjects and F(1, 235) = 3.72, P = 0.055 in all subjects). Post-hoc t-tests confirmed lower levels of AL in IL-1A/B-variant Down subjects (P < 0.05). The distribution of variant IL-1 genes in DS subjects was not different from the general population. However the association between the carriage of the IL-1 rare alleles and periodontitis differed between the Down and non-Down subjects. The carriage of the IL-1 rare alleles in the Down subjects tended to confer a protective effect against loss of periodontal attachment.     

Association of interleukin-1 gene polymorphisms with early-onset periodontitis

Background, aims: Early onset periodontal diseases (EOP) are a group of inflammatory disorders characterised by a rapid rate of periodontal tissue destruction, in young individuals who are otherwise healthy. There is now substantial evidence to suggest that genetic factors play a rôle in the pathogenesis of EOP but the precise nature of these factors remains unclear. Polymorphisms in cytokine genes which may underpin inter‐individual differences in cytokine synthesis and secretion have been associated with other diseases which have an inflammatory pathogenesis, including chronic adult periodontal disease (CAPD). Method: We therefore investigated the frequency of polymorphisms in the genes encoding interleukin‐1β (IL‐1β) and its receptor antagonist (IL‐1RA) in 70 EOP patients, including a subgroup of 21 localised EOP (L‐EOP) patients and 72 periodontally healthy controls. All subjects were of Caucasian heritage and systemically healthy. A single nucleotide polymorphism (SNP) in exon 5 of the IL‐1β gene (IL‐1β⁺³⁹⁵³) was analysed by amplifying the polymorphic region using PCR, followed by restriction digestion with Taq1 and gel electrophoresis. Results: The frequency of IL‐1β genotypes homozygous for allele 1 (corresponding to the presence of a restriction site) of the IL‐1β⁺³⁹⁵³ SNP was found to be significantly increased in EOP patients (χ² test, p=0.025). Upon stratification for smoking status a significant difference was found in the IL‐1β genotype distribution between EOP smokers compared to control smokers (F‐exact test, p=0.02), but not between EOP non‐smokers and control non‐smokers. The IL‐1β 1/1 genotype occurred at a higher frequency in EOP smokers (odds ratio=4.9) compared to control smokers. A variable number tandem repeat polymorphism (VNTR) in intron 2 of the IL‐1RA gene was analysed by amplifying the polymorphic region using PCR and fragment size analysis by gel electrophoresis. There was no evidence for an association of an IL‐1RA genotype with EOP. However the combination of IL‐1β allele 1 and IL‐1RA allele 1 (corresponding to 4 repeats) was associated with EOP (Clump, p=0.01). Conclusions: These findings suggest that an IL‐1β genotype in combination with smoking, and a combined IL‐1β and IL‐1RA genotype are risk factors for EOP and support a role for genetic and environmental factors in susceptibility to EOP.