Association between CBS gene T833C, G919A and 844ins68 polymorphisms in the 8th exon region and coronary artery disease: a meta-analysis.

BACKGROUND: Several studies indicate that the cystathionine ß-synthase (CBS) gene T833C, G919A and 844ins68 polymorphisms in the 8th exon region may be correlated with coronary artery disease (CAD) susceptibility, but the results have been inconsistent and inconclusive. Thus, a meta-analysis was conducted to provide a comprehensive estimate of these associations. METHODS: On the basis of searches in the PubMed, EMBASE, Cochrane Library, Wanfang, VIP, and CNKI databases, we selected 14 case - control studies including 2123 cases and 2368 controls for this meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated accordingly using a fixed-effect or random-effect model. RESULTS: The results indicated an increased risk between the CBS T833C gene polymorphisms and susceptibility to CAD under the dominant model (CC+CT vs. TT: OR = 1.92, 95% CI: 1.11 ~ 3.32), recessive model (CC vs. CT+TT: OR = 1.88, 95% CI: 1.17 ~ 3.03), and homozygous model (CC vs. TT: OR = 2.46, 95% CI: 1.04 ~ 5.83). In these three genetic models, no significant association was identified for CBS G919A (AA+AG vs. GG: OR = 1.48, 95% CI: 0.45 ~ 4.82),(AA vs. AG+GG: OR = 1.58, 95% CI: 0.93 ~ 2.70),(AA vs. GG: OR = 1.66, 95% CI: 0.40 ~ 6.92) or CBS 844ins68 (II+ID vs. DD: OR = 1.04, 95% CI: 0.80 ~ 1.35),(II vs. ID+DD: OR = 1.09, 95% CI: 0.51 ~ 2.36),(II vs. DD: OR = 1.10, 95% CI: 0.51 ~ 2.39). CONCLUSIONS: This meta-analysis suggests that the CBS T833C gene polymorphism is significantly associated with the risk of CAD and it shows a stronger association in Asian populations. Individuals with the C allele of the CBS gene T833C polymorphism might be particularly susceptible to CAD.

Identification and validation of a disulfidptosis-related genes prognostic signature in lung adenocarcinoma.

Disulfidptosis, a newly revealed form of cell death, regulated by numerous genes that has been recently identified. The exact role of disulfidptosis in lung adenocarcinoma (LUAD) still uncertain. Objective of this study was to explore potential prognostic markers among disulfidptosis genes in LUAD. By combining transcriptomic information from Gene Expression Omnibus databases and The Cancer Genome Atlas, we identified differentially expressed and prognostic disulfidptosis genes. By conducting least absolute shrinkage and selection operator with multivariate Cox regression, four disulfidptosis genes were selected to create the prognostic signature. The implementation of the signature separated the training and validation cohorts into groups with high- and low-risk. Subsequently, the model was verified by conducting an independent analysis of receiver operating characteristic (ROC) curves. Further comparisons were made between the two risk-divided groups with regards the tumor microenvironment, immune cell infiltration, immunotherapy response, and drug sensitivity. The signature was constructed using four disulfidptosis-related genes: SLC7A11, SLC3A2, NCKAP1, and GYS1. According to ROC curves, the signature was effective for predicting LUAD prognosis. In addition, the prognostic signature correlated with sensitivity to chemotherapeutic agents and the efficacy of immunotherapy in LUAD. Finally, through external validation, we showed that NCKAP1 are correlated with tumor migration, proliferation, and invasion of LUAD cells. GYS1 affects immune cell, especially M2 macrophage infiltration in the tumor microenvironment. The disulfidptosis four-gene model can reliably predict the prognosis of patients diagnosed with LUAD, thereby providing valuable information for clinical applications and immunotherapy.