Genetic variants in BCL-2 family genes influence the risk of non-syndromic cleft lip with or without cleft palate.

BACKGROUND: The BCL-2 family is crucial for cell death regulation and is involved in development, tissue homeostasis, and immunity. This study aimed to investigate the association between genetic variants in BCL-2 family genes and non-syndromic cleft lip with or without cleft palate (NSCL/P) risk. METHODS: A two-stage case-control study was conducted in this association study. Gene-based analysis using Multi-marker Analysis of GenoMic Annotation was performed in the first stage cohort, which included 565 cases and 1269 controls. A logistic regression model was employed to assess the effect of single nucleotide polymorphisms (SNPs) on susceptibility to NSCL/P. Candidate SNPs were replicated by extra dbGaP case-parent trios. Haploreg, RegulomeDB, and UCSC Genome Browser were used to identify enhancer effects of promising SNPs. Bulk RNA sequencing data obtained from the Gene Expression Omnibus was used to identify co-expressed genes. Single-cell RNA sequencing dataset was used to infer the cell population of the candidate gene. The "Monocle" package was used to analyze the pseudotime cell trajectories. RESULTS: Rs3943258 located in the enhancer region was associated with the risk of NSCL/P (Pmeta = 5.66 × 10-04 ) and exhibited an eQTL effect for BCL2 (P = 3.96 × 10-02 ). Co-expression and pathway enrichment analysis revealed that genes related to Bcl2 were significantly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, and Wnt signaling pathway. Five cell clusters were identified in single-cell RNA sequencing, and Bcl2 was mainly located in the mesenchyme. CONCLUSION: The rs3943258 located within BCL2 was probably related to NSCL/P susceptibility.

The association of aldehyde exposure with the risk of periodontitis: NHANES 2013-2014.

OBJECTIVES: Three distinct models were utilized to investigate the combined impacts of serum aldehyde exposure and periodontitis. MATERIALS AND METHODS: We performed a cross-sectional analysis using data from 525 participants in the 2013-2014 National Health and Nutrition Examination Survey (NHANES). The directed acyclic graphs (DAG) were used to select a minimal sufficient adjustment set of variables (MSAs). To investigate the relationship between aldehydes and periodontitis, we established three models including multiple logistic regression model, restricted cubic spline (RCS) model, and Bayesian kernel machine regression (BKMR) model. RESULTS: After taking all covariates into account, the multiple logistic regression model revealed that elevated concentrations of isopentanaldehyde and propanaldehyde were strongly associated with periodontitis (isopentanaldehyde: OR: 2.38, 95% CI: 1.34-4.23; propanaldehyde: OR: 1.51, 95% CI: 1.08-2.13). Furthermore, the third tertile concentration of isopentanaldehyde was associated with a 2.04-fold increase in the incidence of periodontitis (95% CI: 1.05-3.95) compared to the first tertile concentration, with a P for trend = 0.04. RCS models showed an "L"-shaped relationship between isopentanaldehyde and periodontitis (P for nonlinear association < 0.01), with inflection point of 0.43 ng/mL. BKMR identified a strong connection between mixed aldehydes and periodontitis, with isopentanaldehyde exhibiting the greatest posterior inclusion probability (PIP) with 0.901 and propanaldehyde exhibiting a PIP with 0.775. CONCLUSIONS: Isopentanaldehyde and propanaldehyde are positively associated with the risk of periodontitis. CLINICAL RELEVANCE: Periodontitis may be associated with exposure to mixed aldehyde. This study emphasizes the important role of aldehydes in primary prevention of periodontitis.