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•The FSCN1 gene rs2966447 SNP increased breast cancer susceptibility.•The FSCN1 rs2966447 variant is associated with cancer stages and tumor size.•The FSCN1 rs2966447 variant is ...associated with elevated serum fascin-1 levels.•Serum fascin-1 levels were significantly elevated in advanced-stage breast cancer.•Serum fascin-1 levels were notably associated with tumor stage and nodal status.
Fascin-1 (FSCN1) is recognized as an actin-binding protein, commonly exhibits up-regulation in breast cancer (BC) and is crucial for tumor invasion and metastasis. The existence of FSCN1 gene polymorphisms may raise the potential for developing BC, and there are still no studies focusing on the relationship between the FSCN1 rs2966447 variant and BC risk in Egyptian females. Thus, we investigated the serum fascin-1 levels in BC patients and the association between the FSCN1 rs2966447 variant with its serum levels and BC susceptibility. Genotyping was conducted in 153 treatment-naïve BC females with different stages and 144 apparent healthy females by TaqMan® allelic discrimination assay, whereas serum fascin-1 level quantification was employed by ELISA. The FSCN1 rs2966447 variant demonstrated a significant association with BC susceptibility under all utilized genetic models, cancer stages and estrogen receptor negativity. Also, BC females with AT and TT genotypes had higher serum fascin-1 levels and tumor size than those with the AA genotype. Moreover, serum fascin-1 levels were significantly elevated in the BC females, notably in those with advanced-stages. Furthermore, serum fascin-1 levels were markedly positively correlated with number of positive lymph nodes as well as tumor size. Collectively, these findings revealed that the FSCN1 rs2966447 variant may be regarded as a strong candidate for BC susceptibility. Also, this intronic variant is associated with increased serum fascin-1 levels and tumor size.
Epidemiological studies have shown that exposure to Polycyclic aromatic hydrocarbons (PAHs) is associated with reduced mitochondrial DNA copy number (mtDNA-CN). Long non-coding RNA maternally ...expressed gene 3 (MEG3) is involved in mitochondrial function regulation. However, it is unknown whether single-nucleotide polymorphisms in the MEG3 can regulate the mtDNAcn in PAHs exposed populations. The aim of this study was to examine the effect of MEG3 genetic polymorphisms on the mtDNA-CN in PAHs exposed populations.
We recruited 544 coke oven workers and 238 controls using random cluster sampling. High-performance liquid chromatography was used to detect the concentrations of four OH-PAHs (1-hydroxypyrene 1-OHPyr, 1-hydroxynathalene 1-OHNap, 2-hydroxynathalene 2-OHNap, and 3-hydroxyphenanthrene 3-OHPhe) in urine. The mtDNA-CN of peripheral blood leukocytes was measured using the quantitative polymerase chain reaction method. Sequenom Mass ARRAY matrix-assisted laser desorption/ionization-time of flight mass spectrometry platform was used to detect ten polymorphisms in MEG3.
The OH-PAHs levels in the exposure group were significantly higher than those in the control group (P < 0.001). The mtDNA-CN in the exposure group was significantly lower than that in the control group (P < 0.001). A linear regression model revealed that PAHs-exposure (β 95% confidence interval, CI, −0.428 -0.475, −0.381, P < 0.001), male gender (−0.052 -0.098, −0.005, P = 0.029), genotype TT for MEG3 rs11859 (−0.088 -0.142, −0.035, P = 0.001), and genotype GG for MEG3 rs7155428 (−0.114 -0.210, −0.017, P = 0.021) were associated with decreased mtDNA-CN.
PAHs-exposure, male gender, genotype TT for rs11859, and genotype GG for rs7155428 were risk factors for mtDNA-CN.
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•Flight mass spectrometry platform was established to detect MEG3 polymorphisms.•PAHs exposure induced the mtDNA-CN decrease.•MEG3 rs11859 TT and rs7155428 GG may be risk factors of the reduction of mtDNA-CN.
Antibodies play a crucial role in activating protective immunity against malaria by interacting with Fc-gamma receptors (FcγRs). Genetic variations in genes encoding FcγRs can affect immune cell ...responses to the parasite. In this study, our aim was to investigate whether non-coding variants that regulate FcγR expression could influence the prevalence of Plasmodium falciparum infection. Through bioinformatics approaches, we selected expression quantitative trait loci (eQTL) for FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B genes encoding FcγRs (FCGR), in whole blood. We prioritized two regulatory variants, rs2099684 and rs1771575, located in open genomic regions. These variants were identified using RegVar, ImmuNexUT, and transcription factor annotations specific to immune cells. In addition to these, we genotyped the coding variants FCGR2A/rs1801274 and FCGR2B/rs1050501 in 234 individuals from a malaria-endemic area in Burkina Faso. We conducted age and family-based analyses to evaluate associations with the prevalence of malarial infection in both children and adults. The analysis revealed that the regulatory rs1771575-CC genotype was predicted to influence FCGR2B/FCGR2C/FCGR3A transcripts in immune cells and was the sole variant associated with a higher prevalence of malarial infection in children. In conclusion, this study identifies the rs1771575 cis-regulatory variant affecting several FcγRs in myeloid and neutrophil cells and associates it with the inter-individual capacity of children living in Burkina Faso to control malarial infection.
Background: We aimed to retrospectively review data of pregnant women with the α-fibrinogen Thr331Ala polymorphism; evaluate the relationship between this polymorphism and spontaneous abortion (SA), ...fetal growth restriction (FGR), and intrauterine fetal death (IUFD); and assess the effects of aspirin and/or heparin.
Materials and methods: We examined the outcomes of 29 pregnancies (nine women) in women with the α-fibrinogen Thr331Ala polymorphism. Of these, 16 were untreated, whereas 13 were treated with heparin and/or aspirin.
Results: The live birth rate was significantly higher in the treated group than in the nontreated group (69.2 versus 6.2%; p = .0004). In addition, the prophylactic use of a low dose of aspirin and/or heparin during early pregnancy in women with Thr331Ala may be an effective method for reducing fetal loss in these patients.
Conclusions: This polymorphism interacts with pregnancy to result in poor obstetrical outcomes, but these effects can be mitigated with medical intervention. This study is the first to report outcomes of pregnancies complicated by the Thr331Ala polymorphism, which we believe may cause thrombophilia, SA, and IUFD. This study highlights the need for further research on this polymorphism in pregnancy.
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