Introduction
Periodontitis is a prevalent, chronic, multifactorial, infectious disease that affects the gingiva as well as the tooth’s supporting structures [
1,
2]. Nearly 10% of adults and 30% of individuals above 50 have severe periodontitis [
3,
4]. Periodontitis has been recognized to be linked to obesity [
5,
6], as well as metabolic syndrome [
7,
8]. It is well known that increased visceral fat typically leads to abnormalities in serum lipid profiles [
9,
10], involving elevated levels of LDL cholesterol, HDL cholesterol, TG, and TC. Dyslipidemia is associated with various disease progress as it represents a significant cardiovascular disease (CVD) risk factor [
11‐
14] and is involved in chronic inflammation [
15,
16]. High serum lipid levels have been suggested to contribute to a pro-inflammatory condition that increases oxidative stress, resulting in hyper-reactive molecular species production imbalance with the antioxidant defense that predisposes an individual to infection [
17].
Since 1999, researchers have investigated the correlation among periodontitis as well as serum lipid levels, specifically LDL, HDL, TG, and TC, considering the hypothesis that periodontitis may impact serum lipid levels [
18]. Lately, various investigations have been conducted to explore the correlation between periodontitis and lipid parameters [
17]. However, periodontitis impact on lipid metabolism remains debatable. Many clinical studies have reported a substantial correlation among periodontitis as well as serum lipid levels [
19‐
21]. Conversely, several studies have documented the absence of significant associations among them [
22‐
25]. Considering that there is still uncertainty about this association, further research on serum lipid levels and periodontitis is warranted.
The challenge of establishing causality in observational investigations may be prompted by environmental confounding or reverse causality. The utilization of genetic variants that are associated with the exposure of interest as instrumental variables to explore their effects on outcomes is an effective approach that overcomes certain constraints, commonly referred to as MR methods. At conception, genetic variants are randomly allocated, thereby reducing the impact of environmental confounding on their association with the outcome. Lately, MR methods have been utilized to explore mediated pathways [
26] in which utilizing genetic variants that capture lifetime exposure assists in overcoming biases associated with measurement errors that may hinder observational studies. Therefore, the present study assessed the association between HDL, LDL, TC, and TG serum levels and periodontitis using two MR samples.
Discussion
Numerous observational studies have connected dyslipidemia to periodontitis. However, the causal link remains unknown. In this investigation, two-sample MR analyses were used to comprehensively assess the causality of the association between the four lipid characteristics (HDL, LDL, TC, and TG) and the risk of developing periodontitis. The results revealed no statistically significant association between the HDL, LDL, TG, and TC levels and the periodontitis risk. Because obesity and unfavorable lipid combinations often coexist, statistically non-significant associations remained when we considered confounding factors such as BMI, diabetes, smoking, and alcohol intake. An additional model and MVMR were used to analyze, and similar results were obtained.
Whether lipid metabolism affects periodontitis risk remains controversial. A significant risk factor for developing atherosclerosis and CVD is dyslipidemia [
40]. Notably, HDL cholesterol is recognized for its ability to reverse cholesterol transport, improve endothelial function, and possess antioxidant and anti-inflammatory properties [
41]. A low HDL cholesterol level is an established risk factor for atherosclerosis and future CVD [
42]. The extant body of literature presents divergent findings with respect to the plausible association between periodontitis and serum lipid levels. The study conducted by Korhonen and colleagues revealed a lack of statistically significant association between periodontitis and LDL cholesterol /HDL cholesterol ratio, as well as TC/HDL cholesterol ratio, within a population of Finnish individuals [
43]. Saxlin et al. conducted a study on a large sample size and determined no significant correlation between serum lipid levels and periodontal infection [
44]. Moreover, an earlier meta-analysis [
20] has documented a significant statistical correlation between periodontitis and LDL cholesterol and TG [
45]. Other studies demonstrated that lower serum HDL cholesterol levels are associated with infected gingival abscesses [
46,
47]. However, because of the differences in the periodontitis assessments and the variability in the disease parameters used, substantial heterogeneity was observed in these studies. Meanwhile, periodontitis might lead to dyslipidemia. There is a possibility that these associations are caused by a combination of suboptimal health practices, including inadequate dietary patterns and insufficient oral hygiene practices [
44]. The association between poor dental health habits and high serum cholesterol, TG, and HDL cholesterol supports this conclusion among the young adult Finnish population [
48]. Therefore, a laboratory study is needed to investigate this mechanism in further detail.
The present study findings were consistent with those of earlier studies in which the serum lipids had no correlation with a higher probability of periodontal infection in individuals with average weight. However, in overweight individuals, there was a correlation between serum lipids and the existence of deepened periodontal pockets [
44]. The deleterious effect of lipids on periodontal tissue can be ascribed to the augmented generation of pro-inflammatory cytokines and concomitant suppression of various growth factors, including platelet-derived growth factor, transforming growth factor b-1, and basic fibroblast growth factor, leading to reduced tissue regeneration [
49]. It should be noted that the observed correlation between individuals who are overweight or obese and their lipid composition is likely attributed to residual confounding factors rather than indicating a real relationship among body weight and lipid composition.
Current bidirectional MR study had several advantages. First, using an MR design, the present investigation can largely simulate a randomized controlled trial within an observational context. Randomized control features are a commonly accepted methodology in studies of causality. However, they are frequently deemed costly. MR studies have the ability to effectively eliminate the confounding bias that may arise from the random assignment of SNPs during conception. In contrast to other observational research methods, the MR can evade the reverse causality effects. Second, the present study obtained the summary statistics for periodontitis to calculate the causal relationship with lipid metabolism, and the findings provide evidence for a correlation between periodontitis and lipid metabolism without establishing a causal relationship. Simultaneously, this investigation exhibited certain limitations. Firstly, the study primarily focused on individuals of European descent. The applicability of the results to other racial groups requires additional research. Secondly, while the diagnosis of periodontitis was based on the international ICD code, periodontitis was categorized into four stages according to its severity and treatment complexity. However, data on the stratification of periodontitis severity was unavailable. Thirdly, large-scale, multi-center randomized controlled studies are the gold standard for establishing causal associations. The findings of this study await validation from subsequent research. Fourthly, negative findings of lipid profiles might reflect low statistical power. The lack of statistical power might explain the inconsistent results between lipid profiles and periodontitis, which should be further examined.
In conclusion, this research results indicate that there was no statistically significant impact of periodontitis on the risk of lipid metabolism among European population.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.