白细胞介素-6基因-174G/C、-572C/G多态性与冠心病和慢性牙周炎的相关性的研究

目的研究白细胞介素-6基因-174G/C、-572C/G多态性与冠心病和慢性牙周炎易感性的关系。方法采用病例对照实验设计,选择129例冠心病伴中重度慢性牙周炎患者、47例冠心病患者、131例中重度慢性牙周炎患者和121例健康者,应用聚合酶链反应-限制性内切酶片段长度多态性基因分析方法,比较IL-6基因-174、-572位点基因型和等位基因频率在各组间分布特点。结果IL-6基因-174位点C等位基因在各组检出率极低为0%～0.8%。GG、GC两种基因型和G、C等位基因频率在组间分布差异无统计学意义（P〉0.05）。IL-6基因-572位点CC、GC、GG三种基因型和C、G等位基因频率在健康组和牙周炎组间分布差异无统计学意义（P〉0.05）,在冠心病组和非冠心病组间分布差异有统计学意义（P〈0.05）,G等位基因在冠心病组的检出率明显高于非冠心病组,差异有统计学意义（P〈0.01）。结论IL-6基因-174位点在中国汉族人群中变异率低。-572位点的多态性与慢性牙周炎的易感性无关,与冠心病有关,-572位点G等位基因可能是冠心病的易感标志。     

白细胞介素6基因-572位点多态性与重度慢性牙周炎易感性的相关分析

目的 研究白细胞介素(IL)6基因-572位点(IL-6-572位点)多态性与重度慢性牙周炎敏感性的关系,以期从基因水平探讨慢性牙周炎的遗传学机制. 方法 用聚合酶链反应-限制性片段长度多态性法检测93例重度慢性牙周炎患者和96名健康对照者的IL-6-572位点基因多态性,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 IL-6-572位点CC、CG、GG基因型在牙周炎组和健康对照组的分布频率分别为52.7%、40.9%、6.4%和67.7%、31.3%、1.0%,3种基因型在牙周炎组与对照组的分布差异有统计学意义(P<0.05);等位基因G、C在牙周炎和对照组之间的比例分别为26.9%、73.1%和16.7%、83.3%,其频率分布差异亦有统计学意义(P<0.05).相对于CC基因型,暴露于CG基因型+GG基因型的相对危险度为1.88(95%CI:1.04-3.40,P<0.05). 结论 本组人群患重度慢性牙周炎的易感性与IL-6-572位点基因多态性有关,其风险随等位基因G的增加而显著增加.     

Interleukin-6 promoter polymorphism (-174 G/C) in Indian patients with chronic periodontitis

Recent studies have focused on genetic polymorphism of the interleukin-6 (IL-6) gene, which has led to a better understanding of the intricate interactions between host response, microorganisms, and genetics. Genotype prevalence appears to vary by the race and ethnicity of the population studied. We used a polymerase chain reaction technique to determine the prevalence of single nucleotide polymorphism in IL-6 at position -174 G>C in a population of 30 South Indians. Blood samples were collected from 15 chronic periodontitis patients and 15 healthy controls. The results showed that the G/G genotype was significantly more frequent in the chronic periodontitis group and that the C/C genotype was significantly more frequent in the control group (P = 0.0069 for both). The G allele was more frequent in chronic periodontitis patients (76.67%), whereas the C allele was more frequent in the control group (73.33%). Among chronic periodontitis patients, the odds ratio for having the G allele, as compared with the controls, was 9.04. In this population, the presence of the G/G genotype of IL-6 (-174) might increase susceptibility to chronic periodontitis, whereas the C/C genotype may have a protective effect.     

Association among interleukin-6 gene polymorphism, diabetes and periodontitis in a Chinese population

Objectives:  Diabetics significantly increase risk for periodontitis. Interleukin-6 (IL-6) gene polymorphism may play certain roles in the progression of periodontitis with diabetes. The purpose of this study was to assess the association among IL-6 gene polymorphisms, type 2 diabetes mellitus (T2DM) and chronic periodontitis (CP) in a Chinese population.
Material and methods:  DNA was obtained from 159 patients with CP, 88 patients with T2DM, 110 patients with CP&T2DM and 135 control subjects. The -174/-572/-597 polymorphisms of IL-6 gene were investigated by restriction fragment length polymorphism of polymerase chain reaction products. The results were further confirmed by sequencing. Significance was set at P  < 0.008 after Bonferroni correction.
Results:  Among four groups, CP&T2DM group showed the lowest IL-6-572 CC genotype and C-allele frequencies (54.5% and 74.1%). In this regard, there were significant differences between CP&T2DM group and the control group [ P  = 0.006, odds ratio (OR)  =  0.475, 95% CI: 0.279–0.808 and P  = 0.002, OR = 0.502, 95% CI: 0.319–0.788 respectively]. Logistic regression with adjustment for age, gender, body mass index, smoking and stress showed no significant difference in terms of IL-6-572 genotypes ( P  = 0.058, OR= 0.523, 95% CI: 0.268–1.022).
Conclusions:  The IL-6-572 genotype and allele distributions are unique to subjects with CP&T2DM in a Chinese population.     

Analysis of the interleukin-1 and interleukin-6 polymorphisms in patients with chronic periodontitis. A pilot study

The aim of this study was to analyse whether the interleukin-1 (IL-1) and IL-6 gene polymorphisms were associated with the susceptibility of chronic periodontitis. Genomic DNA was obtained from 20 patients with chronic periodontitis and 31 periodontally healthy subjects. All subjects were of North European heritage. The test subjects were kept in a maintenance program after periodontal treatment but yet showing signs of recurrent disease. Genotyping of the IL-1alpha [+4845C>T], IL-1beta [-3954C>T] and IL-6 [-174G>C] polymorphisms was carried out using an allelic discrimination Assay-by-Design method on ABI PRISM 7900 Sequence Detection System. All genotypes were analyzed using the GeneMapper 2.0 software. A similar distribution of Single Nucleotide Polymorphism (SNP) was seen in both groups. Analysis by logistic regression including gender, IL-1alpha [+4845C>T], IL-1beta [-3954C>T], IL-6 [-174G>C] genotypes, the composite IL-1 genotype, the combination of the composite IL-1 genotype and the IL-6 -174G>C genotype and adjusting for smoking did not result in any statistically significant difference. SNPs in IL-1alpha [+4845C>T], IL-1beta [-3954C>T] and IL-6 [-174G>C] do not seem to increase the susceptibility to chronic periodontitis in this group of subjects.     

Interleukin-6 receptor gene polymorphisms and periodontitis in a non-smoking Japanese population

AIM: The indispensable role of interleukin-6 receptor (IL-6R) in regulating IL-6 responses has been clearly established. We have previously reported that IL6R polymorphisms strongly influenced the serum levels of soluble IL-6R. In this study, we investigated the association between these genetic variations and periodontitis. MATERIAL AND METHODS: Among the seven novel IL6R single-nucleotide polymorphisms (SNPs) reported, we genotyped two important sites: the +48892 A/C in exon 9 and the -183 G/A in the promoter region. The SNP in exon 9 results in Asp-->Ala substitution in the proteolytic cleavage site of IL-6Ralpha. In total, 212 periodontitis cases and 210 healthy controls were genotyped using polymerase chain reaction, restriction fragment length polymorphisms and direct sequencing methods. RESULTS: Analysis of the genotype distribution of the +48892 A/C SNP in periodontitis patients and in controls revealed a suggestive association with aggressive (p = 0.04) and chronic periodontitis (p = 0.04). In addition, the carriage rate for the A allele was significantly higher in chronic periodontitis patients [p = 0.02, odds ratio (OR) = 2.25]. No association was found in the -183 G/A SNP. The two markers were in linkage disequilibrium (LD) (|D'| = 0.53). CONCLUSION: The IL6R+48892 A/C polymorphism could act as a risk factor for periodontitis; however, further association and biological studies are needed.     

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。     

Analysis of tumor necrosis factor-alpha, transforming growth factor-beta, interleukin-10, IL-6, and interferon-gamma gene polymorphisms in patients with chronic periodontitis

BACKGROUND: Cytokine gene polymorphisms may have an impact on the susceptibility to and progression of chronic periodontitis. In this study, we analyzed the -1082 interleukin-10 (IL-10), -308 tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 1 (TGF-beta1) (codons 10 and 25), -174IL-6, and +874 interferon-gamma (IFN-gamma) gene single-nucleotide polymorphisms in a cohort of patients with chronic periodontal disease. METHODS: The diagnosis was made on the basis of standardized clinical and radiographic criteria. A total of 122 adult patients with chronic periodontitis and 114 unrelated, ethnically and age-matched white control subjects were genotyped by a polymerase chain reaction-sequence-specific primer. RESULTS: The number of individuals carrying the -174IL-6 CC genotype was significantly higher in the group of patients than in the control group (odds ratio [OR] = 1.896; 95% confidence interval [CI] = 1.106 to 3.250; P = 0.0283). The TGF-beta1 (codon 25) GG (Arg(25)/Arg(25)) genotype was detected more frequently in control subjects than in periodontitis patients (OR = 0.459; 95% CI = 0.230 to 0.920; P = 0.0421). CONCLUSION: The -174IL-6 and TGF-beta1 (codon 25) single-nucleotide polymorphisms are associated with susceptibility to chronic periodontitis in the population studied.     

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。     

Coronary heart disease and chronic periodontitis: is polymorphism of interleukin‐6 gene the common risk factor in a Chinese population?

Oral Diseases (2011) 17 , 270–276 Objectives: Coronary heart disease (CHD) and chronic periodontitis (CP) both are multifactorial chronic diseases and related to inflammation. Interleukin‐6 (IL‐6) plays an important role in the pathogenesis of inflammatory diseases. The purpose of the study was to investigate the association among IL‐6 gene polymorphisms, CP and CHD susceptibility in a Chinese population. Material and methods: The investigation was conducted as a case‐control study involving 505 individuals: 113 patients with CHD and CP, 84 patients with CHD, 178 patients with CP and 130 control individuals. The polymorphisms of IL‐6 gene were analyzed by polymerase chain reaction‐restriction fragment length polymorphism. Relationships between the distributions of the genotypes and risk factors were also assessed. Results: Mutations at the loci ‐174 G/C, ‐597 G/A of IL‐6 were rare in a Chinese population. No significant difference for IL‐6‐572C/G polymorphism was detected among moderate CP group, severe CP group and control (P = 0.312 and 0.481), significant differences were found between CHD groups and non‐CHD groups (P ≤ 0.001). After adjustment for CHD risk factors, the G allele resulted in an increased risk (OR = 1.676‐1.856), the GG/CG genotype was nearly two times higher risk compared to CC genotype (OR = 2.010‐2.136). Conclusions: IL‐6‐572C/G polymorphism did not correlate with CP susceptibility, but might be a potential risk factor for CHD in a Chinese population.     

白细胞介素-10基因型与墨玉县维吾尔族成人慢性牙周炎易患性的相关性研究

目的 探讨白细胞介素-10（IL-10）基因-597（C/A）位点单核苷酸多态性与新疆维吾尔自治区墨玉县维吾尔族成人慢性牙周炎（CP）之间的相关性。方法 随机选取2013年4—5月本课题组对新疆墨玉县维吾尔族成人进行的口腔健康流行病学调查资料及采集的颊黏膜拭子样本共300例,根据纳入排除标准将其分为健康对照组、轻度CP组和中重度CP组,每组各100例。采用四引物等位基因特异性聚合酶链反应扩增法检测受试者IL-10-597位点基因型和等位基因的分布。采用卡方检验、有序多分类Logistic回归等方法进行统计学分析。结果 IL-10-597基因型及等位基因频率在健康对照组、轻度CP、中重度CP组分布的差异均无统计学意义（P>0.05）;抽取样本人群的年龄与CP具有相关性,55~65岁人群患CP的风险是低于35岁人群的25倍（OR=25.56,P<0.001）。结论 IL-10-597（C/A）位点单核苷酸多态性与维吾尔族成人CP的发病风险无明显相关性。     

Association of interleukin-10 gene promoter polymorphisms with chronic and aggressive periodontitis

Oral Diseases (2012) 18 , 271–279 Objective: Interleukin‐10 gene promoter polymorphisms have been associated with interleukin‐10 decreased production, thereby playing a role in the pathogenesis of periodontitis. This study aimed to investigate whether interleukin‐10 single nucleotide polymorphisms at positions ‐1087(G/A) and ‐597(C/A) are associated with generalised chronic periodontitis and localised aggressive periodontitis. Methods: Genomic DNA samples were isolated from 276 unrelated Jordanian participants. Subjects were categorised into 86 periodontally healthy controls, 105 chronic periodontitis patients and 85 localised aggressive periodontitis patients. Genotype frequencies were calculated, and differences were determined using Pearson chi‐squared test, and odds ratio and 95 % confidence intervals were included. Results: The frequencies of the ‐1087A and ‐597A alleles were significantly more common in chronic periodontitis patients than controls. The A‐positive allele genotypes (GA, AA) at position ‐1087 and A‐positive allele genotypes (CA, AA) at position ‐597 appeared to increase the risk of having chronic periodontitis. No significant differences were observed in the genotype frequencies between localised aggressive periodontitis patients and controls. Conclusions: These findings indicate the possible use of interleukin‐10 single nucleotide polymorphisms as genetic markers in chronic periodontitis patients and further emphasise the molecular differences between chronic periodontitis and aggressive periodontitis.     

广东人群中牙周炎、糖尿病及IL-6-572基因多态性对失牙数的影响

目的 在广东人群中研究牙周炎、糖尿病及IL-6-572基因多态性对失牙数的影响.方法 纳入492例广东籍受试者,完成2型糖尿病和牙周炎的筛查,记录失牙数,并取颊黏膜脱离细胞棉拭子,采用多聚酶链反应-限制性片段长度多态性法测定IL-6-572单核苷酸多态性位点的基因型.用析因方差分析评估人群中牙周炎、糖尿病及IL-6-572基因多态性对失牙的影响.结果 析因方差分析显示广东人群中牙周炎(F=15.631,P=0.000)、糖尿病(F =67.156,P=0.000)及IL-6-572基因多态性(F=6.273,P=0.013)对缺牙数的影响是显著的.同时,IL-6-572基因多态性和糖尿病组合的交互效应显著(F =6.044,P=0.014),含有CG+ GG基因型的糖尿病患者的平均失牙数最多(1.91颗).结论 牙周炎、糖尿病及IL-6-572基因多态性都是影响失牙数的重要因素,含有CG+ GG基因型的2型糖尿病患者可能会失去更多的牙.     

Genetic variations in the human gelatinase A (matrix metalloproteinase-2) promoter are not associated with susceptibility to, and severity of, chronic periodontitis

BACKGROUND: Gelatinase A (matrix metalloproteinase-2 [MMP-2]) has been shown to play an important role in the pathogenesis of several disorders, including periodontal diseases. In this study, we test the hypothesis that variations in this gene influence the development and severity of chronic periodontitis. METHODS: Four promoter polymorphisms (-1575G/A, -1306C/T, -790T/G, and -735C/T) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 149 patients with mild to severe chronic periodontitis and 127 age-matched controls in the Czech population. RESULTS: No significant differences in distribution of the -1575G/A, -1306C/T, and -735C/T variants between periodontitis and control groups were detected in our study. However, a trend to decreased frequency of the -790 GG homozygotes was observed in patients with chronic periodontitis compared to healthy controls (P = 0.036, P (corr) >0.05). Haplotype analysis of four single nucleotide polymorphisms (SNP) in the MMP-2 gene showed no significant association of any haplotype with chronic periodontitis. CONCLUSION: Our findings suggest that polymorphisms in the MMP-2 gene promoter do not contribute significantly to the interindividual periodontitis susceptibility and/or severity in European Caucasians, and they are not regulatory variants in this disease.     

Polymorphisms in the CD14 and IL-6 genes associated with periodontal disease

AIM: To compare the frequencies of cytokine and receptor molecule genotypes in patients with chronic periodontitis with the corresponding frequencies in a reference population and to study the relationship between periodontal disease severity and polymorphisms in the studied genes. SUBJECTS AND METHODS: CD14, IL-6, TNF-alpha, IL-10, IL-1alpha, IL-1beta, and TLR-4 polymorphisms of 51 periodontitis patients were studied using polymerase chain reaction. The genotype frequencies in the periodontitis patients and a reference population (n=178) were compared. Probing pocket depth (PD), periodontal attachment level (AL), and alveolar bone level (BL) were related to the genotypes. RESULTS: No statistically significant differences could be found between the frequencies of the cytokine genotypes in the periodontitis patients and in the reference group. The extent of periodontal disease was higher in subjects with the T-containing genotype of CD14(-260) and the GG genotype of IL-6(-174) when compared with the extent in the rest of the group. Subjects carrying the composite genotype of the above two were most severely affected by periodontal disease. CONCLUSION: According to the present results, an evident association exists between the carriage of the T-containing genotype of CD14(-260) and the GG genotype of IL-6(-174) and the extent periodontal disease.     

Analysis of genetic polymorphisms at the interleukin-10 loci in aggressive and chronic periodontitis

BACKGROUND/AIMS: Different cytokine genotypes have been described in periodontal disease. The aim of the present study was to investigate the genetic association of two previously described interleukin-10 (IL-10) polymorphisms in patients with aggressive (AP) and chronic periodontitis (CP) and to investigate possible associations with clinical manifestations. METHODS: Based on clinical parameters and radiographs, 23 patients with CP and 18 patients with AP were included in the study. Additionally, 21 age-matched healthy subjects served as a control group. Genomic DNA was isolated from whole blood samples and the IL-10 promoter sequences from positions - 597 to - 824 were amplified by polymerase chain reaction (PCR). Polymorphisms were detected by restriction-enzyme cleavage. The A and C alleles at the - 597 position were associated with the T and C alleles at the - 824 position, respectively. Fisher's exact test was used for the statistical analysis. RESULTS: No significant differences were observed in the allele frequencies between controls and AP patients (p = 0.70) or CP patients (p = 0.43), although the previously reported association between allele A at position - 597 and allele T at position - 824 was observed in our population. CONCLUSION: We conclude that the investigated polymorphisms are not associated with periodontal disease.     

Functional gene polymorphisms in aggressive and chronic periodontitis

There is strong evidence that genetic as well as environmental factors affect the development of periodontitis, and some suggestion that aggressive and chronic forms of the disease share the same genetic predisposition. This study addresses the hypothesis that there are both shared and unique genetic associations in these forms of periodontitis. A sample of 51 patients with aggressive disease, 57 patients with chronic disease, and 100 healthy controls was recruited for this study. Ten functional polymorphisms in 7 candidate genes were genotyped. The results show statistically significant (p 相似文献   

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.