Parkhill J M, Hennig B J, Chapple I L, Heasman P A, Taylor J J
Department of Oral Biology, The Dental School, University of Newcastle upon Tyne, UK.
J Clin Periodontol. 2000 Sep;27(9):682-9. doi: 10.1034/j.1600-051x.2000.027009682.x.
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).
We therefore investigated the frequency of polymorphisms in the genes encoding interleukin-1 beta (IL-1 beta) 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-1 beta gene (IL-1 beta+ 3953) was analysed by amplifying the polymorphic region using PCR, followed by restriction digestion with Taq1 and gel electrophoresis.
The frequency of IL-1 beta genotypes homozygous for allele 1 (corresponding to the presence of a restriction site) of the IL-1 beta+3953 SNP was found to be significantly increased in EOP patients (chi2 test, p = 0.025). Upon stratification for smoking status a significant difference was found in the IL-1 beta 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-1 beta 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-IRA 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-1 beta allele 1 and IL-IRA allele 1 (corresponding to 4 repeats) was associated with EOP (Clump, p = 0.01).
These findings suggest that an IL-1 beta genotype in combination with smoking, and a combined IL-1 beta and IL-1RA genotype are risk factors for EOP and support a role for genetic and environmental factors in susceptibility to EOP.
早发性牙周疾病（EOP）是一组炎症性疾病，其特征为在原本健康的年轻个体中牙周组织快速破坏。现在有大量证据表明遗传因素在EOP的发病机制中起作用，但这些因素的确切性质仍不清楚。细胞因子基因多态性可能是个体间细胞因子合成和分泌差异的基础，已与其他具有炎症发病机制的疾病相关，包括慢性成人牙周疾病（CAPD）。
因此，我们调查了70例EOP患者（包括21例局限性EOP（L-EOP）患者亚组）以及72例牙周健康对照者中白细胞介素-1β（IL-1β）及其受体拮抗剂（IL-1RA）编码基因的多态性频率。所有受试者均为白种人且全身健康。通过PCR扩增多态性区域，随后用Taq1进行限制性消化并进行凝胶电泳，分析IL-1β基因外显子5中的单核苷酸多态性（SNP）（IL-1β +3953）。
发现EOP患者中IL-1β +3953 SNP等位基因1纯合的IL-1β基因型频率显著增加（χ2检验，p = 0.025）。根据吸烟状况分层后，发现EOP吸烟者与对照吸烟者之间的IL-1β基因型分布存在显著差异（F精确检验，p = 0.02），但EOP非吸烟者与对照非吸烟者之间无差异。与对照吸烟者相比，EOP吸烟者中IL-1β 1/1基因型出现的频率更高（优势比 = 4.9）。通过PCR扩增多态性区域并用凝胶电泳进行片段大小分析，分析了IL-IRA基因内含子2中的可变数目串联重复多态性（VNTR）。没有证据表明IL-1RA基因型与EOP有关联。然而，IL-1β等位基因1和IL-IRA等位基因1（对应于4个重复）的组合与EOP相关（Clump，p = 0.01）。
这些发现表明，IL-1β基因型与吸烟相结合，以及IL-1β和IL-1RA联合基因型是EOP的危险因素，并支持遗传和环境因素在EOP易感性中的作用。
