Soedarsono N, Rabello D, Kamei H, Fuma D, Ishihara Y, Suzuki M, Noguchi T, Sakaki Y, Yamaguchi A, Kojima T
Computational and Experimental Systems Biology Group, RIKEN, Genomic Sciences Center, RIKEN, Yokohama, Japan.
J Periodontal Res. 2006 Oct;41(5):397-404. doi: 10.1111/j.1600-0765.2006.00874.x.
Aggressive periodontitis (AgP) is a specific type of periodontal disease that is characterized by rapid attachment loss and bone destruction. While attempting to identify genetic polymorphisms associated with AgP, previous research has focused on candidate genes that may be involved in immune responses to microbial infections. In this study, the focus was on single nucleotide polymorphisms (SNPs) in the key mediators of osteoclast differentiation and activation, which involve receptor activator of nuclear factor-kappaB (RANK), RANK ligand (RANKL) and osteoprotegrin (OPG), in the Japanese population. The aim of this study was to evaluate the association of RANK/RANKL/OPG gene polymorphisms with AgP in the Japanese population.
We examined 99 patients with AgP and 89 controls from the Japanese population to explore the possibility of RANK/RANKL/OPG loci as candidate regions associated with the disease. All exons and relevant exon-intron boundaries of these three candidate genes were amplified by polymerase chain reaction (PCR) using 19 primers, followed by direct sequencing. The polymorphisms were identified by comparing the sequences obtained from 48 subjects.
We identified 27 SNPs in RANK, including 10 novel SNPs and seven SNPs each in both RANKL and OPG. A pairwise linkage disequilibrium analysis using the r2 statistic showed that some SNP pairs from the three loci are in tight linkage disequilibrium.
An association analysis with allelotypes showed that SNPs identified in the RANK/RANKL/OPG genes have no significant association with AgP in the Japanese population.
侵袭性牙周炎（AgP）是一种特殊类型的牙周疾病，其特点是附着快速丧失和骨破坏。在试图鉴定与AgP相关的基因多态性时，先前的研究集中在可能参与对微生物感染免疫反应的候选基因上。在本研究中，重点关注日本人群中破骨细胞分化和激活关键介质中的单核苷酸多态性（SNP），这些介质涉及核因子κB受体激活剂（RANK）、RANK配体（RANKL）和骨保护素（OPG）。本研究的目的是评估RANK/RANKL/OPG基因多态性与日本人群中AgP的关联。
我们检查了99例日本AgP患者和89例对照，以探索RANK/RANKL/OPG基因座作为与该疾病相关候选区域的可能性。使用19条引物通过聚合酶链反应（PCR）扩增这三个候选基因的所有外显子和相关外显子-内含子边界，随后进行直接测序。通过比较从48名受试者获得的序列来鉴定多态性。
我们在RANK中鉴定出27个SNP，包括10个新的SNP，在RANKL和OPG中各有7个SNP。使用r2统计量进行的成对连锁不平衡分析表明，来自这三个基因座的一些SNP对处于紧密连锁不平衡状态。
与等位基因型的关联分析表明，在日本人群中，RANK/RANKL/OPG基因中鉴定出的SNP与AgP无显著关联。
