Objective: To evaluate the bidirectional association between periodontitis and Sjögren's syndrome using the Mendelian randomization (MR) method. Methods: Genome-wide association study (GWAS) data of periodontitis (N = 45 563) and Sjögren's syndrome (N = 214 435) were selected to meet the requirements of the same ethnicity and different regions. Inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) tests were used to evaluate the causal effect. Cochran's Q statistics, MR-Egger intercept, MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results. Results: After screening, the GWAS data of Sjögren's syndrome were based on the Finnish region, and the periodontitis GWAS data were based on the UK region, both of which originated from European ancestry. Using IVW (OR = 1.017, 95% CI = 0.956-1.082), MR-Egger (OR = 0.985, 95% CI= 0.956-1.082), and WM (OR =1.021, 95% CI = 0.948-1.099), no causal effect of Sjögren's syndrome on periodontitis was found using any of the three methods. Conversely, no causal effect of periodontitis on Sjögren's syndrome was found (IVW, OR = 1.024, 95% CI = 0.852-1.230; MR-Egger, OR = 0.978, 95% CI = 0.789-1.212; WM, OR = 1.024, 95% CI = 0.846-1.260). The sensitivity analyses indicated that the results were stable and reliable. Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables, which included single nucleotide polymorphisms (SNPs). The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs. No individual SNP was found that significantly affected the results using the leave-one-out method. Conclusion This study does not support a bidirectional causal effect between periodontitis and Sjögren's syndrome.

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.