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Journal, Genetic Engineering &... Nov 2023Early childhood caries is a significant public health concern affecting about 600 million children globally. The etiology of early childhood caries can be explained as... (Review)
Review
BACKGROUND
Early childhood caries is a significant public health concern affecting about 600 million children globally. The etiology of early childhood caries can be explained as an interplay between genetic and environmental factors. Single nucleotide polymorphisms are the most common variations in the human genome. Genetic variations of immune response genes can modify the defense response of the host, and alter the susceptibility to bacterial colonization of the oral cavity and early childhood caries. The aim of this systematic review is to identify genetic variants of immune response genes associated with early childhood caries.
RESULTS
A total of 7124 articles were identified by conducting an elaborate search across various electronic databases and genome-wide association studies databases. Subsequent to exclusion at various stages, fifteen articles qualified to be included into the present review. Risk of bias assessment was done with the Q-genie tool. Quantitative synthesis revealed that the odds ratio for TT and CC genotypes of rs11362 was 1.07 (0.67-1.71) and 1.16 (0.84-1.60), respectively. Gene-based analysis revealed a statistically significant association between variants of tumor necrosis factor-alpha gene and T-cell receptor alpha variable 4 locus with early childhood caries. Gene clustering showed the presence of three functional clusters. To comprehend the protein-protein interaction, the bioinformatic tool of "Search Tools for the Retrieval of Interacting Genes and Proteins" was used. Among the biological processes and the reactome pathways, complement activation through the lectin pathway showed the highest strength of association with early childhood caries. To understand the interaction and functionality of the genes, "gene function prediction using Multiple Association Network Integration Algorithm" was used, which revealed that the genes were linked by physical interaction (39.34%) and through co-expression (34.88%).
CONCLUSIONS
Genotype TT of rs7217186 of arachidonate 15-lipoxygenase gene was a risk factor for early childhood caries. Multiple genetic variants of T-cell receptor alpha variable 4 locus and tumor necrosis factor-alpha gene were associated with increased susceptibility to early childhood caries. Polymorphisms of genes regulating the lectin pathway of complement activation can modify the susceptibility to early childhood caries.
PubMed: 37971556
DOI: 10.1186/s43141-023-00566-x -
International Journal of Rheumatic... Jul 2022Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Smaller sample size and complex nature of the disease pathogenesis has made it challenging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Smaller sample size and complex nature of the disease pathogenesis has made it challenging to perform well-powered genetic investigations. We performed a systematic review based meta-analysis in GPA to investigate the genetic susceptibility conferred by non-human leukocyte antigen (non-HLA) candidate genes.
METHODS
A systematic review was performed using web-based literature search and eligible studies were included following inclusion-exclusion criteria. Studies were evaluated for their quality of evidence and study outcome was assessed using the Newcastle-Ottawa Scale and Grades of Research, Assessment, Development and Evaluation tools. Reviewer's agreement was accessed through Cohen's κ value. Meta-analyses were performed using RevMan 5 tool. Meta-odds ratio (meta-OR) and Z test P value were evaluated to estimate the genetic susceptibility for each of the variants.
RESULTS
Eighteen studies were found eligible and 7 genetic variants from only 4 genes, namely CTLA4, PRTN3, SERPINA1 and PTPN22 could be studied for meta-analysis. rs231775-G (49-G) (Meta-OR = 1.42 [1.14-1.76]; P = .001) of CTLA4 and rs7151526-A (Meta-OR = 2.70 [1.51-4.85]; P = .0008) of SERPINA1 were confirmed to be predisposing alleles, and rs5742909-C (318-C) (Meta-OR = 0.65 [0.44-0.97]; P =.03) of CTLA4 was found to be protective for GPA. In concordance with the genetic association of rs7151526-A, serological marker for the same variant "Z" allele of SERPINA1 was found to be predisposing (Meta-OR = 12.60 [5.01-31.68]; P < .00001) for GPA.
CONCLUSION
Genetic variants confirmed in this study play critical roles in T-cell mediated immune function and could be significantly implicated in GPA. Molecular pathology studies are warranted to confirm their role. These markers could be used for efficient patient classification and disease management.
Topics: Alleles; CTLA-4 Antigen; Genetic Predisposition to Disease; Granulomatosis with Polyangiitis; Humans; Myeloblastin; Protein Tyrosine Phosphatase, Non-Receptor Type 22; alpha 1-Antitrypsin
PubMed: 35656856
DOI: 10.1111/1756-185X.14354