Qiu Feng, Shao Wei, Qin Xue, Xu Ran, Lu Hua
Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China.
Affiliated Hospital of Jiangnan University, Comprehensive Building, No. 1000, Hefeng Road, Binhu District, Wuxi City, 214125, Jiangsu Province, China.
Sci Rep. 2025 Apr 9;15(1):12196. doi: 10.1038/s41598-025-87040-5.
Clonal hematopoiesis (CH) is an age-associated phenomenon characterized by the proliferation of blood cells carrying somatic mutations. Recent studies suggest a potential link between CH and periodontitis, but the causal relationship remains unclear. A two-sample Mendelian randomization (MR) analysis was implemented, examining whether CH phenotypes are causally associated with periodontitis. CH phenotypes included overall clonal hematopoiesis (CH-overall), CH with a DNMT3A mutation (CH-DNMT3A), CH with a TET2 mutation (CH-TET2), large clones (CH-large), and small clones (CH-small). Genetic instruments were derived from genome-wide association studies, and the inverse-variance weighted (IVW) method was the primary analytical approach. Sensitivity analyses and reverse MR were also performed to ensure robustness. MR analysis demonstrated a significant association between CH-DNMT3A and periodontitis (odds ratio: 0.084, 95% CI: 0.007-0.972, P = 0.047), suggesting a protective role. No significant associations were found for other CH phenotypes. Reverse MR analyses showed no statistical evidence of a bidirectional relationship between periodontitis and any CH phenotype. Additionally, the analyses showed no signs of pleiotropy or heterogeneity that could confound the results. Our findings suggest a novel protective role for DNMT3A-mutated CH in periodontitis. Further research is warranted to explore the mechanisms underlying this association.
克隆性造血（CH）是一种与年龄相关的现象，其特征是携带体细胞突变的血细胞增殖。最近的研究表明CH与牙周炎之间可能存在联系，但因果关系仍不清楚。我们进行了一项两样本孟德尔随机化（MR）分析，以检验CH表型是否与牙周炎存在因果关联。CH表型包括总体克隆性造血（CH-总体）、携带DNMT3A突变的CH（CH-DNMT3A）、携带TET2突变的CH（CH-TET2）、大克隆（CH-大）和小克隆（CH-小）。基因工具来自全基因组关联研究，逆方差加权（IVW）方法是主要的分析方法。我们还进行了敏感性分析和反向MR以确保结果的稳健性。MR分析表明CH-DNMT3A与牙周炎之间存在显著关联（优势比：0.084，95%置信区间：0.007-0.972，P = 0.047），提示其具有保护作用。其他CH表型未发现显著关联。反向MR分析未发现牙周炎与任何CH表型之间存在双向关系的统计学证据。此外，分析未显示可能混淆结果的多效性或异质性迹象。我们的研究结果表明，DNMT3A突变的CH在牙周炎中具有新的保护作用。有必要进一步研究以探索这种关联背后的机制。
