Fassmann Antonin, Holla Lydie Izakovicova, Buckova Dana, Vasku Anna, Znojil Vladimir, Vanek Jiri
Department of Pathological Physiology, Clinic of Stomatology, Medical Faculty and Centre for Mathematical Modelling, Masaryk University Brno, Czech Republic.
J Periodontal Res. 2003 Aug;38(4):394-9. doi: 10.1034/j.1600-0765.2003.00661.x.
Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease.
In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin alpha (LT-alpha) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects.
The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the LT-alpha (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT-alpha 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and LT-alpha) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01).
Our data suggest that combined genotypes composed of the TNF-alpha and LT-alpha gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population.
牙周炎是一种炎症性疾病，可导致不可逆的附着丧失、骨质破坏并最终导致牙齿脱落。肿瘤坏死因子（TNF）是一种多能促炎细胞因子，能够诱导组织破坏和骨质吸收，与牙周病的发病机制有关。
在本研究中，我们调查了慢性牙周炎与TNF基因座中两个先前描述的双等位基因多态性之间的关联：TNF-α基因5'启动子区域-308位的G到A转换以及淋巴毒素α（LT-α）基因第一内含子（+252A/G位）的NcoI限制性片段长度多态性（RFLP）。从132例慢性牙周炎患者以及114名年龄和性别匹配的无关对照受试者中获取基因组DNA。
TNF-α（-308G/A）多态性本身与慢性牙周炎无关联，而LT-α（+252A/G）基因型的频率分布在患者和参照组之间显示出统计学上的显著差异。慢性牙周炎患者组中携带LT-α 1/1基因型的个体比例（0.8%）显著低于对照组（8.8%）（P < 0.0094，校正P < 0.05）。然而，通过应用蒙特卡罗方法进行模拟发现，对照组和患者组之间联合基因型（TNF-α和LT-α）频率存在显著差异（P < 0.01）。
我们的数据表明，由TNF-α和LT-α基因多态性组成的联合基因型可能影响慢性牙周炎的易感性。我们还表明，比较这两个基因，LT-α基因第一内含子中NcoI多态性的1/1基因型是一个更具信息量的标志物，它可能是我们人群中对抗慢性牙周炎的保护性遗传因素之一。
