Noack B, Görgens H, Hempel U, Fanghänel J, Hoffmann Th, Ziegler A, Schackert H K
Department of Conservative Dentistry, Dresden University of Technology, Medical Faculty, Fetscherstrasse 74, 01307, Dresden, Germany.
J Dent Res. 2008 Oct;87(10):958-63. doi: 10.1177/154405910808701017.
Cathepsin C (CTSC) mutations are known to cause Papillon-Lefèvre syndrome. The aim of this study was to examine the association of CTSC genotype with susceptibility to non-syndromic aggressive periodontitis. The CTSC gene was analyzed in 110 persons with generalized aggressive periodontitis in comparison with 78 control individuals, after identifying different variants in a cohort of 100 persons. Five out of 19 discovered variants were included in this association study, representing 5 single-nucleotide polymorphism groups in tight linkage disequilibrium. The relevance of genotypes on enzyme function was examined. The carrier frequency of the missense variant p.I453V was significantly increased in persons with disease compared with healthy control individuals (17.3% vs. 6.4%, p < 0.05). CTSC activity in leukocytes from individuals harboring this variant was significantly reduced (119.8 Delta OD/min*10(5) cells, 95% confidence interval 17.4-174.9, p = 0.018). No influence of promoter variants was found on mRNA expression. The results support the hypothesis that CTSC gene variants contribute to increased susceptibility in generalized aggressive periodontitis.
已知组织蛋白酶C（CTSC）突变会导致帕皮永-勒费夫尔综合征。本研究的目的是检测CTSC基因型与非综合征型侵袭性牙周炎易感性之间的关联。在100人队列中确定不同变异后，对110例广泛性侵袭性牙周炎患者和78例对照个体的CTSC基因进行了分析。本关联研究纳入了19个发现的变异中的5个，代表了处于紧密连锁不平衡状态的5个单核苷酸多态性组。研究了基因型对酶功能的相关性。与健康对照个体相比，错义变异p.I453V的携带者频率在疾病患者中显著增加（17.3%对6.4%，p<0.05）。携带该变异个体白细胞中的CTSC活性显著降低（119.8吸光度变化/min*10(5)细胞，95%置信区间17.4-174.9，p=0.018）。未发现启动子变异对mRNA表达有影响。结果支持CTSC基因变异导致广泛性侵袭性牙周炎易感性增加这一假说。
