Christian-Albrechts-University, Institute for Clinical Molecular Biology, Kiel, Germany.
J Clin Periodontol. 2012 Apr;39(4):315-22. doi: 10.1111/j.1600-051X.2011.01846.x. Epub 2012 Jan 18.
Involvement of TLR2 in the pathophysiology of periodontitis has widely been discussed, but hitherto, no validated genetic associations were reported. Previous association studies lacked sufficient statistical power and adequate haplotype information to draw unambiguous conclusions. The aim of this study was to comprehensively investigate TLR2 linkage disequilibrium (LD) regions for their potential associations with periodontitis in two large analysis populations of aggressive (AgP) and chronic periodontitis (CP) of North West European descent.
The study population comprised 598 AgP patients, 914 CP patients and 1804 healthy controls. Analysis of TLR2 LD regions was performed with haplotype tagging SNPs (tagSNPs) using SNPlex and TaqMan genotyping assays. Genotypic, dominant, multiplicative, and recessive genetic models were tested. The genotypes were adjusted for the covariates smoking, diabetes, and gender. Resequencing was performed by Sanger technology.
Upon covariate adjustment and correction for multiple testing, no tagSNPs showed significant associations with AgP or CP. Targeted resequencing of exon 3 in 47 AgP cases identified carriership of two common and three rare variants.
Common LD regions of TLR2 do not show genetic associations with periodontitis in the North West European population. Resequencing of exon 3 could not identify disease-associated rare variants in TLR2.
TLR2 参与牙周炎的病理生理学已被广泛讨论，但迄今为止，尚未报道经过验证的遗传关联。先前的关联研究缺乏足够的统计效力和充分的单倍型信息，无法得出明确的结论。本研究的目的是全面研究 TLR2 连锁不平衡 (LD) 区域，以评估其与北欧血统侵袭性牙周炎 (AgP) 和慢性牙周炎 (CP) 的潜在关联。
研究人群包括 598 名 AgP 患者、914 名 CP 患者和 1804 名健康对照者。使用 SNPlex 和 TaqMan 基因分型检测试剂盒，通过单倍型标签 SNP (tagSNP) 分析 TLR2 LD 区域。对 TLR2 的单倍型、显性、相乘和隐性遗传模型进行了测试。对基因型进行了吸烟、糖尿病和性别等混杂因素的调整。采用 Sanger 技术进行重测序。
在调整了混杂因素并进行了多重检验校正后，没有 tagSNP 与 AgP 或 CP 具有显著相关性。对 47 例 AgP 病例的外显子 3 进行靶向重测序，发现两种常见和三种罕见变异的携带者。
TLR2 的常见 LD 区域与北欧人群的牙周炎无遗传关联。外显子 3 的重测序未能鉴定出 TLR2 中与疾病相关的罕见变异。
