A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis
A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis
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DOI：
10.1111/jcpe.12749
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发表时间：
2017-10-01
影响因子：
6.7
通讯作者：
Schaeefer, Arne S.
中科院分区：
文献类型：
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作者：
Munz, Matthias;Chen, Hong;Schaeefer, Arne S.
目的：纤溶酶原基因（PLG）的内含子变异rs 4252120与侵袭性牙周炎（AgP）和动脉粥样硬化相关。在这里，我们研究了染色体区域跨越PLG协会与慢性牙周炎（CP）和AgP.Materials和方法：PLG候选人rs 4252120的协会进行了测试，在德国的病例对照样本的1,419 CP病例使用基因分型检测hCV 11225947和4,562对照，基因分型与人类Omni BeadChips。用HumanOmni BeadChips对德国和荷兰的AgP病例（N = 851）和对照（N = 6，836）样本进行基因分型。北美CP样本（N = 2，681例，1，823例对照）先前在全基因组人类SNP阵列6.0上进行了基因分型。基因型进行插补（软件Impute v2），并进行关联测试，使用添加剂的遗传模型调整性别和smoking.Results：RS 4252120与CP不相关。然而，PLG下游的单倍型块与rs 4252120不连锁不平衡（r（2）= 0.08）与AgP（rs 1247559; p = 0.002，比值比[OR] = 1.33）和CP（p = 0.02，OR = 1.15）相关。该位点也与成骨细胞中PLG的表达显著相关（p = 6.9 × 10（-5））。结论：我们的研究结果支持PLG基因变异在牙周炎病因学中的作用。
Aim: 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.Materials and Methods: 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.Results: Rs4252120 was not associated with CP. However, a haplotype block downstream of PLG and not in linkage disequilibrium with rs4252120 (r(2) =.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 x 10(-5)).Conclusions: Our findings support a role of genetic variants in PLG in the aetiology of periodontitis.