Department of Periodontology, Institute of Dental, Oral and Maxillary Medicine, Charité - University Medicine Berlin, Berlin, Germany.
Institute for Integrative and Experimental Genomics, University Medical Center Schleswig-Holstein - Campus Lübeck, Lübeck, Germany.
J Clin Periodontol. 2017 Oct;44(10):962-970. doi: 10.1111/jcpe.12749. Epub 2017 Sep 11.
The intronic variant rs4252120 in the plasminogen gene (PLG) is known to be associated with aggressive periodontitis (AgP) and atherosclerosis. Here, we examined the chromosomal region spanning PLG for associations with both chronic periodontitis (CP) and AgP.
The association of PLG candidate rs4252120 was tested in a German case-control sample of 1,419 CP cases using the genotyping assay hCV11225947 and 4,562 controls, genotyped with HumanOmni BeadChips. The German and Dutch sample of AgP cases (N = 851) and controls (N = 6,836) were genotyped with HumanOmni BeadChips. The North American CP sample (N = 2,681 cases, 1,823 controls) was previously genotyped on the Genome-Wide Human SNP Array 6.0. Genotypes were imputed (software Impute v2), and association tests were performed using an additive genetic model adjusting for sex and smoking.
Rs4252120 was not associated with CP. However, a haplotype block downstream of PLG and not in linkage disequilibrium with rs4252120 (r = .08) was associated with both AgP (rs1247559; p = .002, odds ratio [OR] = 1.33) and CP (p = .02, OR = 1.15). That locus was also significantly associated with PLG expression in osteoblasts (p = 6.9 × 10 ).
Our findings support a role of genetic variants in PLG in the aetiology of periodontitis.
纤溶酶原基因（PLG）中的内含子变异 rs4252120 已知与侵袭性牙周炎（AgP）和动脉粥样硬化有关。在这里，我们研究了跨越 PLG 的染色体区域与慢性牙周炎（CP）和 AgP 的关联。
使用基因分型检测 hCV11225947 对来自德国的 1419 例 CP 病例的候选基因 PLG rs4252120 进行关联测试，同时对 4562 例对照进行基因分型，使用 HumanOmni BeadChips 进行基因分型。使用 HumanOmni BeadChips 对德国和荷兰的 AgP 病例（N=851）和对照（N=6836）进行基因分型。北美 CP 样本（N=2681 例病例，1823 例对照）先前使用基因组高通量 SNP 阵列 6.0 进行基因分型。使用 Impute v2 软件进行基因型推断，并使用加性遗传模型进行关联测试，调整性别和吸烟因素。
rs4252120 与 CP 无关。然而，PLG 下游的一个单倍型块与 rs4252120 没有连锁不平衡（r=0.08），与 AgP（rs1247559;p=0.002，优势比[OR]1.33）和 CP（p=0.02，OR1.15）都有关联。该基因座与成骨细胞中 PLG 的表达也显著相关（p=6.9×10）。
我们的研究结果支持 PLG 遗传变异在牙周炎发病机制中的作用。
