白细胞介素-4基因-590C/T多态性与慢性牙周炎易感性的Meta分析

目的:通过文献评价探讨白细胞介素-4(interleukin-4,IL-4)-590C/T基因多态性与慢性牙周炎(chronic periodontitis,CP)易感性之间的关系.方法:检索8个数据库,搜集国内外有关病例对照研究文献.根据种族进行亚组分析,采用Meta分析评估IL-4基因多态性与CP的关联性,同时进行发表偏倚的检验和异质性分析,并对结果进行敏感性分析 . 结果:最终有8个研究纳入系统评价,病例组628例,健康对照组717例 . Meta分析结果显示,IL-4基因-590C/T位点等位基因频率及基因多态性与研究人群CP易感性间均无显著相关性.进一步亚组分析显示,对于C等位基因而言,携带T等位基因增加了高加索人患CP的风险(C vs.T:OR=0.71,95％CI=0.56～0.89);高加索人种CP的易感性与-590C/T位点多态性显著相关(C vs.T:OR=0.71,95％CI=0.56～0.89;CC vs.CT:OR =0.60,95％CI=0.38～0.94;隐性模型CC vs.CT+TT:OR =0.61,95％CI=0.42～0.88),即高加索人中携带CC基因型者较携带CT与TT基因型者患CP风险减少39％,而亚洲人CP的易感性与该基因无显著相关性.结论:IL-4基因-590C/T位点多态性与高加索人CP易感性有一定相关性.这一结论尚需要大规模、多种族的流行病学研究加以验证.     

IL-1β基因3954C＞T位点多态性与侵袭性牙周病易感性的Meta分析

目的:通过Meta分析进一步探究IL-1β基因3954C＞T位点多态性改变与侵袭性牙周炎的相关性.方法:检索PubMed,Embase,CNKI和万方数据库中有关IL-1β基因3954C＞T位点多态性与侵袭性牙周炎易感性相关文献,以OR值和95％的可信区间为效应指标,应用STATA 11.0软件进行Meta分析,并对发表偏倚及敏感性分析进行检验.结果:纳入22个病例对照研究,共计965例侵袭性牙周炎患者和1234例对照,Meta分析结果显示,总人群中,IL-1β基因3954C＞T位点多态性与牙周病风险之间没有显着关联(T vs.C:OR=0.966,95 ％CI=0.696～1.341:CT vs.CC:OR=0.936,95％CI=0.761～1.151;TT vs.CC:OR=0.892,95％CI=0.464～1.715;CT+TT vs.CC:OR=1.026,95％CI=0.795-1.323;TT vs.CC+CT:OR=0.864,95％CI=0.436、1.713).相应的亚组分析未发现IL-1β基因3954C＞T位点多态性和侵袭性牙周炎易感性无显著相关性.结论:IL-1β基因3954C＞T位点多态性多态性可能与侵袭性牙周炎的发生无关.     

白细胞介素-4基因-590C／T多态性与慢性牙周炎的相关性研究

目的研究白细胞介素-4（interleukin-4,IL-4）基因-590C／T多态性与慢性牙周炎易感性的关系。方法采用病例对照试验设计,聚合酶链反应一限制性内切酶片段长度多态性基因分析方法,比较104例慢性牙周炎患者（慢性牙周炎组）和106例牙周健康者（健康对照组）IL-4基因-590位点基因型和等位基因分布特点。结果IL-4基因-590位点C、T等位基因频率（X2=0．771,P=0．380）及基因型频率（X2=1．904,P=0．386）在两组间分布差异无统计学意义。结论IL-4基因-590位点的多态性与汉族人群慢性牙周炎的易感性无明显相关性。     

白细胞介素13基因-1112C/T多态性与慢性牙周炎的相关性研究

目的 探讨白细胞介素13(interleukin-13,IL-13)基因启动子区-1112C/T多态性与慢性牙周炎易感性的相关性.方法 采用病例对照试验设计,慢性牙周炎患者110例(慢性牙周炎组)和牙周健康者106例(健康对照组),聚合酶链反应-限制性片段长度多态性方法检测两组患者IL-13基因-1112位点基因型和等位基因分布特点.结果 IL-13基因-1112位点C、T等位基因频率(x2=0.886,P=0.347)及基因型频率(x2=1.982,P=0.371)在两组间分布差异无统计学意义.结论 IL-13基因-1112位点的多态性与汉族人群慢性牙周炎的易感性无明显相关性.     

转化生长因子β1基因-509位点多态性与重度慢性牙周炎易感性的关系

目的 探讨转化生长因子β1(transforming growth factor beta-1,TGF-β1)基因-509位点多态性与重度慢性牙周炎易感性的关系,以期从基因水平探讨牙周炎发病的遗传学机制.方法 用聚合酶链反应-限制性片段长度多态性方法检测102例重度慢性牙周炎患者(牙周炎组)和102名健康对照者(健康对照组)的TGF-β1基因-509位点,比较两组间此位点基因型分布和等位基因频率的差异.结果 TGF-β1基因-509位点CC、CT、TT基因型在牙周炎组和健康对照组的分布频率分别为44.1%(45/102)、47.1%(48/102)、8.8%(9/102)和29.4%(30/102)、51.0%(52/102)、19.6%(20/102),两组人群基因型分布频率差异有统计学意义(P＜0.05);等位基因C、T在牙周炎组和健康对照组分布频率分别为67.6%(138/204)、32.4%(66/204)和54.9%(112/204)、45.1%(92/204),两组人群的等位基因分布频率差异亦有统计学意义(P＜0.05),C等位基因携带者患重度慢性牙周炎的风险是T等位基因的1.718倍(OR=1.718,95%CI:1.148～2.569).结论 TGF-β1基因-509位点多态性与重度慢性牙周炎的发病具有相关性,C等位基因可能是重度慢性牙周炎的遗传易感基因.     

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-6基因-572C/G多态性与慢性牙周炎的相关性研究

目的研究白细胞介素-6（interleuk in-6,IL-6）基因启动子区域-572C/G位点基因多态性与慢性牙周炎易感性的关系。方法采用病例对照试验设计,轻中度牙周炎组87例,重度牙周炎组72例,健康对照组90例,收集颊粘膜拭子,使用聚合酶链反应—限制性内切酶片段长度多态性基因分析的方法,检测各组IL-6-572位点基因型和等位基因分布。结果 IL-6基因-572C/G位点G等位基因的检出率在健康组是14.4%,轻中度牙周炎组是14.4%,重度牙周炎组是20.1%。等位基因频率在患者和健康者之间无统计学差异（P=0.287）。CC基因型在各组的分布分别是健康组73.3%,轻中度牙周炎组71.3%,重度牙周炎组63.9%,各组之间差异无统计学意义（P=0.308）。结论 IL-6基因-572位点多态性与汉族人群慢性牙周炎的易感性无明显相关。     

转化生长因子-β1和白细胞介素-10单核苷酸多态性与复发性口腔溃疡易感性的研究

目的 研究转化生长因子-β1（TGF-β1）-509T/C位点与白细胞介素-10（IL-10）-1082A/G位点的单核苷酸多态性与复发性口腔溃疡（RAU）易感性的相关性。方法 采用限制性片段长度多态性-聚合酶链式反应（RFLPPCR）RFLPPCR）法和序列特异性引物-聚合酶链式反应（SSP-PCR）法对138例RAU患者和124例健康对照者进行TGF-β1-509位点与IL-10-1082位点的单核苷酸多态性的检测分析,用比值比（OR）和95%可信区间（95%CI）估计相对危险度。结果 TGF-β1-509位点与IL-10-1082位点在基因型频率与等位基因频率的分布上,病例组与正常对照组之间均存在明显差异（P<0.05）。TGF-β1-509位点基因型CT（OR=1.231,95%CI=0.702~2.160）与TT（OR=2.482,95%CI= 1.250~4.927）为高风险基因型,T等位基因为高风险等位基因（OR=1.465,95%CI=1.036~2.074）。IL-10-1082位点基因型AG（OR=1.391,95%CI=0.808~2.396）与GG（OR=4.165,95%CI=1.944~8.924）为高风险基因型,G等位基因为高风险等位基因（OR=2.134,95%CI=1.474~3.089）。结论 TGF-β1-509位点与IL-10-1082位点是RAU患者的易感基因位点。TGF-β1-509位点携带T等位基因患RAU的风险性是携带C等位基因者的1.465倍。IL-10-1082位点携带G等位基因患RAU的风险性是携带A等位基因者的2.134倍。     

白细胞介素基因多态性与汉族广泛型侵袭性牙周炎易感性的相关性研究

目的探讨白细胞介素10（interleukin-10,IL-10）启动子区域基因多态性与广泛型侵袭性牙周炎易感性的关系。方法收集30例广泛型侵袭性牙周炎患者和30名健康对照者的颊黏膜拭子,提取基因组DNA,采用PCR-RFLP方法检测IL-10基因启动子-1082G/A、-819C/T、-592A/C位点基因多态性,比较广泛型侵袭性牙周炎患者和健康对照组中等位基因频率和基因型分布。结果IL-10-1082G/A、-819C/T、-592A/C位点等位基因频率和基因型分布在患者和对照组之间差异无统计学意义（P〉0.05）。结论IL-10启动子区基因多态性与汉族人群广泛型侵袭性牙周炎易感性无明显相关关系。     

IL-6、IL-6R和IL-4多态性与上海地区汉族人群慢性牙周炎患者的关联研究

目的 研究IL-6、IL-6R和IL-4基因组单核苷酸多态性（single nucleotide polymorphisms,SNPs）与上海地区汉族人群慢性牙周炎患者的相关性。方法 应用TaqMan荧光实时定量PCR方法,对128例牙周正常者和198例中度以上慢性牙周炎患者的IL-6 -572G/C、IL-6R 48892A/C和 IL-4 -590C/T等3个单核苷酸多态性位点进行分析。应用SPSS 17.0软件包对数据进行χ2检验分析。结果 分析显示这3个位点的基因型频率与等位基因频率在牙周正常组和慢性牙周炎组间的分布差异均无显著性。结论 IL-6 -572G/C、IL-6R 48892A/C和 IL-4 -590C/T基因组单核苷酸多态性位点与上海地区汉族人群的慢性牙周炎易感性无显著相关性。     

Single-nucleotide polymorphisms in the IL-4 and IL-13 promoter region in aggressive periodontitis

INTRODUCTION: IL-4 and IL-13 polymorphisms have been shown to influence the susceptibility to systemic diseases. In this study, possible associations between the IL-4 -590 C-->T, IL-4 -34 C-->T, IL-13 -1112 C-->T and IL-13 -1512 A-->C promoter polymorphisms were investigated in subjects with generalized aggressive periodontitis (AgP) compared with healthy individuals. MATERIAL AND METHODS: Fifty-eight patients with diagnosis of generalized AgP and 51 matched healthy controls participated in the study. Blood samples were collected and DNA isolated. Molecular analyses were performed by PCR-RFLP in a blind fashion. Genotype and allele frequencies among study groups were compared using Fisher's exact test (alpha value: 0.05). Pearson's chi(2) test was used for analysis of Hardy-Weinberg equilibrium. RESULTS: The frequency of the IL-4 -590 T/T and IL-4 -34 T/T genotypes differed significantly between groups (p=0.05, 0.02, respectively), although the allele frequencies were similar. There was a higher frequency of the IL-4 -590 T/T and IL-4 -34 T/T genotypes in patients with AgP compared with controls. The genotype and allele frequencies of the IL-13 polymorphisms did not differ between groups. CONCLUSIONS: This study demonstrated an association between the IL-4 -590 T/T and IL-4 -34 T/T genotypes and AgP. Further research is necessary to prove if there is an association of these polymorphisms with AgP, and if the polymorphisms have a functional effect.     

Interferon-gamma and interleukin-12 gene polymorphisms and their relation to aggressive and chronic periodontitis and key periodontal pathogens

BACKGROUND: The gene polymorphisms interferon-gamma (IFN-gamma) 874 T/A and interleukin (IL)-12 1188 A/C have been associated with the altered production of cytokines. Therefore, they might be indicative of the occurrence of chronic periodontitis (CP) or aggressive periodontitis (AgP) and the prevalence of key periodontal pathogens. For this purpose, we analyzed these polymorphisms in subjects with generalized AgP or generalized CP. Moreover, we assessed the relationship between these polymorphisms and five periodontopathic bacteria. METHODS: A total of 124 unrelated German white subjects with periodontitis (AgP=72 and CP=52) and 74 periodontitis-free subjects were studied. Gene polymorphisms were determined by polymerase chain reaction with sequence-specific primers. Subgingival bacteria were molecular biologically analyzed using multiplex polymerase chain reaction and reverse hybridization. The distributions of alleles and genotypes were calculated by the chi(2) test with Yates correction. Risk factor analyses were carried out by logistic regression considering established confounders for periodontitis. RESULTS: Allele and genotype frequencies of both investigated polymorphisms were not significantly different between subjects with periodontitis and periodontitis-free controls. However, in the total study group, IL-12 AA-positive subjects had a significantly higher bleeding index than individuals who expressed IL-12 CC (68.2% versus 50.0%, P=0.025). Moreover, IFN-gamma AA carriers had a decreased odds ratio (OR) for the individual presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) (OR=0.39, P=0.012) after adjustment for age, gender, smoking, and probing depth. IFN-gamma TA predisposed an individual to infection with Prevotella intermedia (OR=2.15, P=0.019). CONCLUSION: Although a relationship between the bleeding index and the presence of bacteria was shown, IFN-gamma and IL-12 polymorphisms are not suitable diagnostic features for AgP and CP.     

The association of interleukin-4 haplotypes with chronic periodontitis in a Czech population

BACKGROUND: Cytokine gene polymorphisms are known to influence the susceptibility and disease course of many chronic disorders. Recently, interleukin (IL)-4 gene polymorphisms were associated with aggressive periodontitis. The aim of this study was to test differences in the distribution of the IL-4 alleles, genotypes, and haplotypes between patients with chronic periodontitis (CP) and healthy controls in a Czech population. METHODS: The association study was conducted using an age- and smoking status-matched case-control design in patients with CP (n = 194) and healthy controls (n = 158) using the polymerase chain reaction-restriction fragment length polymorphism methods for the -590C/T, -33C/T, and intron 3 variable number tandem repeat (VNTR) variants of the IL-4 gene. RESULTS: No significant differences between patients and controls were found in allele and genotype frequencies of all three polymorphisms. Nevertheless, complex analysis revealed significant differences in haplotype frequencies between the groups (P = 0.005). The haplotype T(-590)/T(-33)/allele 2 VNTR (70 base pairs)(2) of the IL-4 gene was significantly more frequent in patients with CP than in controls (17.0% versus 11.0%; odds ratio = 1.85; 95% confidence interval: 1.19 to 2.87). CONCLUSION: The three polymorphisms in the IL-4 gene act in a cooperative fashion and suggest that the high-production IL-4 haplotype was associated with an increased risk for CP in the Czech population.     

Polymorphisms of TLR4 but not CD14 are associated with a decreased risk of aggressive periodontitis

OBJECTIVE: To study whether there is an association between the frequency of functional polymorphisms in the toll-like receptor 4 (TLR4) and cluster differentiation 14 (CD14) genes and periodontitis. METHODOLOGY: Genotyping for the TLR4 single-nucleotide polymorphisms (SNPs) Asp299Gly, Thr399Ile and the CD14 SNPs -159 and -1359 was completed for subjects with periodontal disease compared with control subjects. Two disease populations were investigated: 73 subjects with aggressive periodontitis (AgP; 28 males, 45 females) and 95 males with chronic periodontitis (CP). The TLR4 and CD14 polymorphisms were determined using SNaPshot primer extension with capillary electrophoresis. Comparison of allele and genotype frequencies for each polymorphism was by Fisher's exact test or chi2 analysis. RESULTS: The TLR4 Asp299Gly genotype was present in a significantly (p=0.026) lower proportion of AgP subjects (5.5%) compared with control subjects (16.3%). The unadjusted odds ratio for the Asp299Gly genotype to be associated with AgP was 0.30, 95% confidence interval 0.10-0.91. No differences were found in the prevalence of the TLR4 Asp299Gly genotype in men with CP (18.9%) compared with an age-matched control group with no evidence of periodontitis (17%). In addition, there was no difference in the distribution of the CD14 polymorphisms in either the AgP or CP populations studied compared with controls. CONCLUSION: It is concluded that in West European Caucasians, the Asp299Gly TLR4 gene polymorphism is associated with a decreased risk of AgP but not CP. Promoter polymorphisms of the CD14 gene, however, did not influence susceptibility to inflammatory periodontitis in the population cohorts studied.     

Association Between Interleukin‐4 Gene −590 C/T, −33 C/T,and 70‐Base‐Pair Polymorphisms and Periodontitis Susceptibility: A Meta‐Analysis

Background: Several studies have investigated the association between interleukin (IL)‐4 gene ?590 C/T, ?33 C/T, or 70–base pair (70‐bp) polymorphisms and periodontitis susceptibility but with conflicting results. Hence, a meta‐analysis was conducted to explore whether these polymorphisms are associated with periodontitis susceptibility. Methods: A comprehensive literature search was conducted of PubMed, Embase, Scopus, ScienceDirect, and Web of Science up to April 5, 2014. After the eligible studies were identified, data were extracted and quality‐assessed before performing the meta‐analysis. Results: The meta‐analysis included 23 eligible case‐control studies from 11 articles involving 12 studies of the ?590 C/T polymorphism (1,220 cases and 2,039 controls), five of the ?33 C/T polymorphism (715 cases and 967 controls), and four of the 70‐bp polymorphism (426 cases and 506 controls). The meta‐analysis showed that none of these IL‐4 gene polymorphisms were significantly associated with periodontitis susceptibility in all study participants. However, subgroup analysis showed that the IL‐4 ?590 T allele (odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.02 to 1.42, P = 0.03) and TT genotype (OR = 1.68, 95% CI = 1.05 to 2.67, P = 0.03) were associated with periodontitis in whites. Conclusions: Based on current evidence, the IL‐4 ?33 C/T and 70‐bp polymorphisms were not associated with an increased risk of periodontitis. However, the IL‐4 ?590 T allele and TT genotype were associated with increased risk of periodontitis in whites.     

NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive periodontitis: a case-control association study

INTRODUCTION: Neutrophils (PMN) in aggressive periodontitis (AgP) patients have been reported to be hyperactive especially with regards to superoxide production. Polymorphisms in genes influencing PMN function have been proposed as candidate risk factors for AgP. The aim of this study was to test the association of specific gene polymorphisms affecting PMN functions with AgP. MATERIALS AND METHODS: Two hundred and twenty-four patients with confirmed diagnosis of AgP and 231 subjects with healthy periodontium took part in the study. A blood sample was collected from subjects and genotypes for p22phox (CYBA) NADPH oxidase, FP, Fcalpha and Fcgamma receptors were analysed in a blind fashion. RESULTS: The C242T p22phox NADPH oxidase T allele was significantly associated with AgP in a multiple logistic regression model adjusting for confounders, and this was observed for all subjects [p = 0.002, odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.27-2.83] and Caucasians (p = 0.009, OR=2.07, 95% CI = 1.20-3.59). Concomitant presence of C242T p22phox NADPH oxidase T allele and FcgammaRIIIb NA1 homozygosity was associated with the generalized AgP phenotype in Caucasians (p = 0.001, OR = 30.35, 95% CI = 3.81-241.97). CONCLUSIONS: C242T p22phox NADPH oxidase and FcgammaR polymorphisms may predispose to AgP through a modulation of neutrophil superoxide production.     

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.