Correlation of vitamin D receptor gene (ApaI) polymorphism with periodontitis: A meta‐analysis of Chinese population

Abstract Many studies have tried to elucidate the connection between vitamin D receptor (VDR) gene (ApaI) polymorphism and periodontitis; however, so far there is no consensus. To further assess the impact of ApaI polymorphism on periodontitis risk, we have conducted a meta‐analysis of Chinese population. Relevant literatures were searched according to PubMed and Chinese database in January 2019. The strength of correlation was evaluated by combining odds ratio (ORs) and 95% confidence interval (CIs). Six case–control studies were identified with inclusion criteria, including 734 cases of periodontitis and 687 controls. Based on the overall analysis, the VDR ApaI polymorphism was not due to the risk of periodontitis in all models. Subgroup analysis showed that the risk of periodontitis in North China was significantly reduced. To sum up, the study shows that VDR‐ApaI polymorphism may be connected with a lower risk of periodontitis in northern China. It is suggested that inferential studies should be conducted in other ethnic groups.

and (d) meta-analyses, letters, meeting abstracts, reviews, and editorial articles.

| Data extraction
Two reviewers extracted data from each study. The dispute was stable through discussion. Screen the headlines and abstracts of all potentially relevant manuscripts to determine relevance. If the headline and abstract are ambiguous, check the whole article carefully. We collected the information as follows from each study: first author's surname; publication year; type of periodontitis; source of control; geographic region (s); sample capacity; and quantity of subjects with VDR ApaI genotype.

| Statistical analysis
The statistics of correlation were evaluated by combining odds ratio (ORs) and 95% confidence interval (CIs). Z test was applied to determine the significance of combined ORs and 95% CIs. The heterogeneity was measured by Q statistics. In cases of heterogeneity, the random-effect model was selected to aggregate 95% CIs-distributed ORs, and then, the fixed-effect model was applied. Sensitivity analysis was evaluated by contrasting the results of the fixed-and random-effect models. In addition to comparing all subjects, stratified analysis was conducted according to geographic region(s), control source and type of periodontitis. Statistical analyses were handled by the University City of Texas Stata Corporation (version 10.0; Stata Corporation). p < .05 was considered as the statistical significance.

| Description of included studies
Totally 62 studies that examined the relationship between the VDR polymorphisms and the risk of periodontitis were distinguished after document duplication was deleted in different databases ( Figure 1).
Fifty articles were excluded after the first screening of titles and abstracts. Of the 12 potential related articles identified for comprehensive research, seven were excluded because of duplication, and no control group or genotype data were available. Finally, five articles (including six case-control studies) (Li et al., 2008;Ma, Zhang, Huang, & Han, 2011;Shao, 2013;Wang et al., 2009;Zhang et al., 2005) (Table 1).

| Meta-analysis
The primary results are enumerated (Table 2). Firstly, heterogeneity analysis was carried out. In the overall analysis, there was no correlation between VDR ApaI polymorphism and periodontitis risk (

| Sensitivity analysis
Statistics analysis was conducted by comparing the results of fixed-effect and random-effect models. Except for the allele control model, all significant corresponding ORS remained unchanged, indicating that the outcomes of the meta-analysis were relatively steady (Table 2).

| D ISCUSS I ON
As an inflammatory disease, periodontitis is most often caused by microorganisms. As a multifactorial disease, previous studies have shown that the susceptibility of individuals to periodontal disease depends partly on genetic factors. The connection between the VDR ApaI polymorphism and periodontitis cause has been attached the attention by many researchers. One meta-analysis showed that CP patients have a markedly higher frequency of the AA genotype of ApaI (OR, 52.20; 95% CI, 51.39-53.48; p < .001) (Deng et al., 2011); however, another meta-analysis suggested that the ApaI polymorphism has no significant association with susceptibility to periodontitis (CP/AP) (Chen, Li, Zhang, & Wang, 2012).
As a result, we proceeded this analysis to more accurately estimate the relationship between VDR-ApaI polymorphism and periodontitis susceptibility among Chinese population. The analysis involved Lots of studies are conducted to explore the correlation between VDR ApaI variants and periodontitis previously. Several studies (El Jilani et al., 2015;Karasneh et al., 2013;Naito et al., 2007) show that the VDR ApaI polymorphism was related to an increased risk of developing CP, while the opposite results are found with severe generalized CP in Turkish patients (Gunes et al., 2008 Finally, owing to the limitations of funnel charts, which require a large series of studies, we could not assess publication bias in this meta-analysis.
All in all, the meta-analysis suggests that VDR ApaI polymorphism may be connected with a reduced cause of periodontitis in northern China; however, much more researches should be investigated in the future to verify our findings.

ACKNOWLEDGMENTS
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

CO N FLI C T O F I NTE R E S T
The authors declare that they do not have any conflict of interest.

E TH I C A L A PPROVA L
This study does not involve any human or animal testing, and all analyses are based on previously published studies; thus, no ethical review and patient consent are required.