Patients on dialysis tend to present an imbalance in their immune-inflammatory response, which could predispose them to the evolution of inflammatory diseases, such as PD. Yue et al.9 confirmed that periodontal treatment, through scaling and root planning, could reduce the systemic levels of IL-6 and TNF-α in patients on hemodialysis. This highlights the importance of understanding the influence of genetic polymorphisms on kidney progression and periodontal destruction
It has been observed that the presence of pro-inflammatory cytokines could increase the prevalence of several diseases and thus compromise the general condition of patients with CKD. Balakrishnan et al.10 evaluated the influence of IL-6 and TNF-α polymorphisms with comorbidity indices and the general status of patients on hemodialysis. The investigators found, regarding IL-6, that the C allele resulted in the suppression of transcription of this cytokine, while its increase was related to the G allele and the GG genotype, resulting in longer and more severe hospitalizations. In our study, although we did not delve into systemic and hospitalization issues, we did not find any differences between the case and control groups. However, in patients on hemodialysis, the absence of the C allele and genotype GG relates to the worsening of oral alterations, such as PD. As for TNF-α, for the aforementioned authors, there is a greater chance of worsening comorbidities related to allele A and genotypes GA or AA in patients on hemodialysis.
In contrast, Singh et al.4 reported that only the AA genotype of TNF-α is related to the initiation and progression of kidney injury and the need for hemodialysis. While Genctoy et al.11 reported that this development was associated only with the GA genotype, this study had a sample size of only 22 patients. In disagreement with the three reported studies, our study found no difference between the hemodialysis and healthy groups regarding the TNF-α -308 G/A polymorphism.
As for periodontal changes, unlike the results found in the studies of Parkar et al.12 and Chhokra et al.13, who found worsening of periodontal clinical parameters in hemodialysis patients, in our study, no statistically significant difference was found between the groups, as well as in the study by Marakoglu et al.14 A probable explanation would be that patients in the control group actively searched the dental department because they complained about their oral health, while patients on hemodialysis were invited to participate in the research without first reporting any discomfort.
Another factor to consider is that there were no statistically significant differences between the two groups in terms of the allelic and genotypic distribution of single-base polymorphisms (SNPs) of IL-6 and TNF, which may influence the worsening of PD in only one of the groups. Song, et al. 15, in their meta-analysis, investigated whether IL-6 and TNF-α polymorphisms confer susceptibility to PD in ethnically different populations and, in agreement with our study, found a higher prevalence of the G allele of the IL-6–174 G/C polymorphism in Brazilians with periodontitis. However, while the meta-analysis reported a higher association of allele A of the TNF-α -308 A/G polymorphism with periodontal disease in Brazilians, Turks, and Asians, the present study did not verify such an association. Notably, we observed a low prevalence of allele A in patients with periodontitis.
Zhao et al.16 conducted a study to evaluate the association between PD and the IL-6 -174G/C polymorphism and reported that the G allele was related to increased susceptibility to PD, while the CC genotype was associated with low IL-6 production. In our study, despite showing no statistically significant difference, the G allele was more prevalent in patients with PD in both the control and hemodialysis groups. The CC genotype, which is considered protective, was detected in only one patient in each group studied, which may explain the periodontal health status in both groups.
Although studies that seek to infer a relationship between inflammatory processes, genetic polymorphisms, and their influence on the aggravation of some diseases are increasing in number, many of the reported results have been controversial. While a review by Barros et al.17 concluded that there is a wide variation in the results related to periodontitis and polymorphism, studies such as Tevillato et al.18 correlated the IL-6 GG genotype with greater periodontal destruction. In contrast, D'Aiuto et al.19 reported that the C allele increased serum IL-6 levels and worsened PD. According to Holla et al.20 the SNPs did not show statistically significant results related to the presence of periodontitis, as in the present study.
The divergence of the results in the literature may also be related to the severity of periodontal destruction. When stratifying the control and hemodialysis groups according to the stage of PD, we found that the absence of the IL-6 allele C was more prevalent in patients with grade 3 and 4 disease, which suggests that this allele would have a protective function in PD, in agreement with the results of D'Aiuto et al.19. However, Moreira et al.21also evaluating PD in a Brazilian population and found that the higher the IL-6 expression, the greater the severity of PD and that the absence of the G allele would have a protective action.
As for TNF-α, studies such as Dag et al.22, found increased serum levels of TNF-α in the gingival crevice fluids of patients with PD on hemodialysis, which suggests that periodontitis affects the levels of this cytokine both systemically and orally. However, Menezes et al.23, when studying the association of the TNF-α -308G/A polymorphism, suggested that this polymorphism was not associated with periodontitis in the Brazilian population, in agreement with the findings of this study. We suggest that further studies should be carried out and correlated with other SNPs that have not been previously studied.
As for PD, a reported by Zhao et al.16 that investigated the existence of a range of cytokine polymorphisms that may act together to aggravate periodontitis identified other risk factors, such as oral hygiene, age, habits, and smoking. Thus, it is necessary to consider the interaction between genetics, age, and environmental exposure to explain the effects of a given polymorphism. Since the studies found in the literature involve different populations with different selection criteria and classifications, the results can also vary substantially.
It is worth pointing out that discussions of themes are primarily found in older works, and this represents a certain difficulty in investigating more up-to-date data. Reinforcing this, there is a need for more studies in this area.
From our results, we can conclude that genetic polymorphisms and their influence on the replication of pro-inflammatory cytokines may determine the worsening of the course of some diseases, such as PD and CKD. However, while the TNF-α-308 A/G polymorphism was not related to the diseases studied, that of IL-6 -174 G/C showed statistically significant results, in which the presence of the GG genotype and the absence of the C allele were related to more severe forms of PD in patients on hemodialysis.