Trombone A P F, Cardoso C R, Repeke C E, Ferreira S B, Martins W, Campanelli A P, Avila-Campos M J, Trevilatto P C, Silva J S, Garlet G P
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, São Paulo University, FMRP/USP, São Paulo, Brazil.
J Periodontal Res. 2009 Oct;44(5):598-608. doi: 10.1111/j.1600-0765.2008.01166.x. Epub 2008 Dec 11.
Inflammatory cytokines such as tumor necrosis factor-alpha are involved in the pathogenesis of periodontal diseases. A high between-subject variation in the level of tumor necrosis factor-alpha mRNA has been verified, which may be a result of genetic polymorphisms and/or the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola (called the red complex) and Aggregatibacter actinomycetemcomitans. In this study, we investigated the effect of the tumor necrosis factor-alpha (TNFA) -308G/A gene polymorphism and of periodontopathogens on the tumor necrosis factor-alpha levels in the periodontal tissues of nonsmoking patients with chronic periodontitis (n = 127) and in control subjects (n = 177).
The TNFA -308G/A single nucleotide polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism analysis, whereas the tumor necrosis factor-alpha levels and the periodontopathogen load were determined using real-time polymerase chain reaction.
No statistically significant differences were found in the frequency of the TNFA -308 single nucleotide polymorphism in control and chronic periodontitis groups, in spite of the higher frequency of the A allele in the chronic periodontitis group. The concomitant analyses of genotypes and periodontopathogens demonstrated that TNFA -308 GA/AA genotypes and the red-complex periodontopathogens were independently associated with increased levels of tumor necrosis factor-alpha in periodontal tissues, and no additive effect was seen when both factors were present. P. gingivalis, T. forsythia and T. denticola counts were positively correlated with the level of tumor necrosis factor-alpha. TNFA -308 genotypes were not associated with the periodontopathogen detection odds or with the bacterial load.
Our results demonstrate that the TNFA -308 A allele and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased tissues of nonsmoking chronic periodontitis patients and consequently are potentially involved in determining the disease outcome.
肿瘤坏死因子-α等炎性细胞因子参与牙周疾病的发病机制。已证实肿瘤坏死因子-α mRNA水平存在较高的个体间差异，这可能是基因多态性和/或牙周病原体（如牙龈卟啉单胞菌、福赛坦氏菌、具核梭杆菌（称为红色复合体）和伴放线聚集杆菌）存在的结果。在本研究中，我们调查了肿瘤坏死因子-α（TNFA）-308G/A基因多态性和牙周病原体对非吸烟慢性牙周炎患者（n = 127）和对照受试者（n = 177）牙周组织中肿瘤坏死因子-α水平的影响。
采用聚合酶链反应-限制性片段长度多态性分析研究TNFA -308G/A单核苷酸多态性，而使用实时聚合酶链反应测定肿瘤坏死因子-α水平和牙周病原体负荷。
尽管慢性牙周炎组A等位基因频率较高，但在对照组和慢性牙周炎组中，TNFA -308单核苷酸多态性的频率未发现统计学上的显著差异。对基因型和牙周病原体的联合分析表明，TNFA -308 GA/AA基因型和红色复合体牙周病原体与牙周组织中肿瘤坏死因子-α水平升高独立相关，当两个因素同时存在时未观察到相加效应。牙龈卟啉单胞菌、福赛坦氏菌和具核梭杆菌计数与肿瘤坏死因子-α水平呈正相关。TNFA -308基因型与牙周病原体检测几率或细菌负荷无关。
我们的结果表明，TNFA -308 A等位基因和红色复合体牙周病原体与非吸烟慢性牙周炎患者病变组织中肿瘤坏死因子-α水平升高独立相关，因此可能参与决定疾病结局。
