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类风湿关节炎和牙周病是否存在共同的遗传风险标志物?一项病例对照研究。

Are There Any Common Genetic Risk Markers for Rheumatoid Arthritis and Periodontal Diseases? A Case-Control Study.

机构信息

Department of Operative Dentistry and Periodontology, Martin Luther University Halle-Wittenberg, Germany.

出版信息

Mediators Inflamm. 2019 Feb 12;2019:2907062. doi: 10.1155/2019/2907062. eCollection 2019.

Abstract

BACKGROUND

Several studies suggest that there is a biologically plausible connection between rheumatoid arthritis (RA) and periodontal diseases (PD). Both disorders are characterized as multifactorial diseases potentially sharing common risk factors. Based on the inflammatory nature of RA and PD, the impact of genetic variations of genes of the immune system on both diseases was studied in this study.

MATERIALS AND METHODS

We conducted a case-control study ( = 201) comparing 101 RA patients suffering from periodontal disease of different severities (no/mild PD vs. severe PD) with 100 systemically healthy controls without RA and severe PD. The genotype, allele, and haplotype distributions of 22 SNPs of 13 pro- and anti-inflammatory cytokines were assessed applying sequence-specific PCR.

RESULTS

Evaluating the impact of cytokine SNPs in RA, we identified the G allele of rs1801275 in IL4R ( = 0.043) and the G allele of rs361525 in TNF ( = 0.005) as disease-associated risk factors in bivariate analyses. In multivariate analyses, these significant associations could not be proven. The A allele of rs2430561 in IFN was indicative for severe periodontitis among the patients with rheumatoid arthritis ( = 0.039). Investigating the impact of rs2430561 in IFN on comorbidity using binary logistic regression analyses, the A allele was confirmed as an independent risk factor for severe periodontal disease and RA ( = 0.024).

CONCLUSIONS

These results emphasize the association of genetic variations in proinflammatory cytokines (TNF and IFN) and cytokine receptor (IL4R) and RA and periodontal diseases. In multivariate analyses, the A allele of IFN was proven to be a significant marker of RA and PD comorbidities. The study broadens the knowledge about disease-specific differences in genetic composition and provides an improved understanding of a possible association of both diseases.

摘要

背景

多项研究表明,类风湿关节炎(RA)和牙周病(PD)之间存在生物学上合理的联系。这两种疾病都具有多因素疾病的特征,可能具有共同的危险因素。基于 RA 和 PD 的炎症性质,本研究研究了免疫系统基因的遗传变异对这两种疾病的影响。

材料和方法

我们进行了一项病例对照研究(n=201),比较了 101 名患有不同严重程度牙周病的 RA 患者(无/轻度 PD 与重度 PD)与 100 名无 RA 和重度 PD 的系统性健康对照者。采用序列特异性 PCR 评估 13 种促炎和抗炎细胞因子的 22 个 SNP 的基因型、等位基因和单倍型分布。

结果

评估细胞因子 SNP 在 RA 中的影响时,我们发现 IL4R 中的 rs1801275 的 G 等位基因(=0.043)和 TNF 中的 rs361525 的 G 等位基因(=0.005)在双变量分析中是疾病相关的危险因素。在多变量分析中,这些显著的关联无法得到证明。IFN 中的 rs2430561 的 A 等位基因在 RA 患者中预示着严重的牙周炎(=0.039)。使用二元逻辑回归分析研究 rs2430561 在 IFN 中对合并症的影响,证实 A 等位基因是严重牙周病和 RA 的独立危险因素(=0.024)。

结论

这些结果强调了促炎细胞因子(TNF 和 IFN)和细胞因子受体(IL4R)中的遗传变异与 RA 和牙周病的关联。在多变量分析中,IFN 的 A 等位基因被证明是 RA 和 PD 合并症的重要标志物。该研究拓宽了对遗传组成中疾病特异性差异的认识,并提供了对两种疾病可能关联的更好理解。

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