侵袭性牙周炎患者及其亲属白细胞介素-1基因多态性的研究

目的:研究侵袭性牙周炎(AgP)患者及其亲属白细胞介素-1(interleukin-1,IL-1)基因多态性与AgP易感性的关系.方法:收集66个核心家系共180名成员,进行全口牙周检查、摄全口根尖片并拍摄口内彩色照片,AgP先证者的诊断参照1999年牙周病分类法,其亲属的诊断参照1999年牙周病分类法和现状与回顾性相结合的评分标准作出评估诊断.提取研究对象外周静脉血基因组DNA,应用聚合酶链反应-限制性片段长度多态性的方法,分析IL-1A+4845,IL-1B-511位点的单核苷酸多态性(single nucleotide polymorphisms,SNP)及IL-1RN第二内含子中的可变数目重复序列(variable number tandem repeats,VNTR)的多态性,采用多因素Logistic回归模型进行各组之间基因型/等位基因分布差异的比较,同时还采用以家系为基础的关联检验的方法(family-based association test)进行关联分析.结果:未发现IL-1基因各位点等位基因/基因型在AgP先证者与其亲属之间、以及亲属各组之间的分布差异有统计学意义(P＞0.05).以家系为基础的关联检验表明,IL-1B-511和IL-1A+4845等位基因1在加性、显性及隐性3种遗传模型检验中,P值均大于0.05,即未发现IL-1基因各位点的多态性与AgP存在具有统计学意义的关联.但是,当把所有AgP患者按照全口牙槽骨吸收特点进行亚型分型并经Logistic回归模型调整了年龄、性别和吸烟状况后发现,在IL-1B-511位点,以局限型破坏为主的AgP患者A1A1基因型的频率比非AgP患者显著升高(43.8% vs 22.8%,OR=7.32,95% CI=1.84～29.11,P=0.005),等位基因A1的分布差异也有统计学意义(71.9% vs 41.2%,OR=3.64,95% CI=1.55～8.58,P=0.002);而广泛型AgP患者与非AgP患者两组之间差异无统计学意义(基因型A1A1:P=0.88,等位基因A1:P=0.64).结论:IL-1B-511位点的SNP可能与以局限型破坏为主的AgP的易感性有关,但仍需要在更大样本量中验证.

Interleukin-1 family polymorphisms in aggressive periodontitis patients and their relatives

OBJECTIVE: To study whether interleukin-1( IL-1 )genotype and/or alleles were associated with aggressive periodontitis (AgP) patients and their relatives. METHODS: Sixty-six AgP nuclear families including 66 probands and their 114 relatives were recruited. All probands were diagnosed as AgP according to 1999 classification of periodontal diseases and conditions, the diagnoses of their relatives were using a system of assessment (including the current and retrospective diagnosis and reported case history). Anti-coagulated peripheral blood samples were collected from all of the 180 subjects, and DNA was extracted from each blood sample. Single nucleotide polymorphisms (SNPs) at IL-1A +4845 and IL-1B j 511 were analyzed by PCR-RFLP assay. The polymorphism of a variable number of tandem repeat (VNTR) in intron 2 of IL-1RN was detected by PCR amplification and fragment size analysis. The distributions of genotypes and/or alleles in all groups were analyzed by logistic regression analysis. Data were also analyzed using the family-based association test. RESULTS: The frequency of all markers (at IL-1A +4845 and IL-1B -511 and VNTR) showed no association wih AgP in relatives (P>0.05). Tests of association by Family-Based Association Test showed no difference in the distribution of the allele 1 of IL-1B-511 under all three genetic models tested (Additive: Z=0.389, P=0.6969; Dominant: Z=0.089, P=0.9287; Recessive: Z=0.089, P=0.9287). The distribution of the allele 1 of IL- 1A+4845 also showed no significant difference under all three models (P>0.05). But when all AgP patients were stratified by the clinical subtype, the frequencies of A1A1genotype and allele 1 at IL-1B-511 were significantly increased in the localized subtype AgP patients compared to unaffected (genotype: 43.8% vs 22.8%,OR=7.32,95% CI=1.84-29.11,P=0.005; allele 1: 71.9% vs 41.2%,OR=3.64,95% CI=1.55-8.58,P=0.002), while no significant difference was observed between the generalized subtype and the unaffected (genotype: P=0.88, allele: P=0.64). CONCLUSION: The polymorphism of IL-1B-511 may have an effect on the susceptibility of localized AgP in Chinese population. It should be tested in larger family samples.