RESUMEN
Polymorphisms in Toll-like receptors (TLRs) genes have been associated with cervical cancer, but some inconsistencies were found in the results. The present study aimed to investigate the role of polymorphisms in the TLRs genes in cervical cancer, through meta-analysis and bioinformatics analysis. Searches were performed in PubMed, Science Direct, Scopus and Web of science online databases until November 2020. For bioinformatics analysis, we used SNP2TFBS, Raptor-X, MUpro, Gene Expression Profiling Interactive Analysis (GEPIA). The results of meta-analysis showed that the +1196T (rs4986791 TLR4), +7764T (rs1927911 TLR4), -1486C (rs187084 TRL9) +2848A (rs352140 TRL9) alleles carriers and -2604G/G (rs10759931 TLR4), -1237C/C (rs5743836 TRL9) genotypes were associated with an increased risk for cervical cancer. The bioinformatics analysis revealed that the -1237T>C (rs5743836) and -1486T>C (rs187084) polymorphisms can affect the transcription factors binding sites (RELA, NFKB1 and THAP1) in the TLR9 gene, and the +2848G>A (rs352140) polymorphism seems to alter the structure and stability of TLR4 protein. Additionally, using GEPIA, was observed a significantly high of IL-1ß, IL-18 and TNF-α expression in cervical cancer tissues compared to normal tissues. These finds indicate that polymorphisms in the TLR4 and TLR9 genes can affect intracellular signaling and, consequently, change the patterns of the immune response, leading to an increased risk for cervical cancer.
Asunto(s)
Receptor Toll-Like 4 , Receptor Toll-Like 9 , Neoplasias del Cuello Uterino , Proteínas Reguladoras de la Apoptosis/genética , Proteínas de Unión al ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inmunidad , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 4/genética , Receptor Toll-Like 9/genética , Neoplasias del Cuello Uterino/genéticaRESUMEN
Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools.Methods: Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case-control studies.Results: A total of 35 relevant case-control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs in IL-17A (rs2275913, rs3748067); IL-17 F (rs763780); IL-12A (rs568408); IL-12B (rs3212227); TNFA (rs1800629, rs361525); IL-1B (rs16944); IL-6 (rs1800795); IL-10 (rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of the TNFA and IL-10 genes through the MZF1 (TNFA -308 G > A and IL-10 - 1082A>G) and ZNF263 (TNFA -238 G > A) transcription factors binding.Conclusion: Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer.
Asunto(s)
Alphapapillomavirus/fisiología , Citocinas/genética , Infecciones por Papillomavirus/genética , Lesiones Precancerosas/genética , Lesiones Intraepiteliales Escamosas de Cuello Uterino/genética , Neoplasias del Cuello Uterino/genética , Biología Computacional , Femenino , Predisposición Genética a la Enfermedad , Humanos , Infecciones por Papillomavirus/inmunología , Polimorfismo de Nucleótido Simple , Riesgo , Lesiones Intraepiteliales Escamosas de Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/inmunologíaRESUMEN
Serotonin and nitric oxide seem to be involved in Dengue virus infection. The aim of this study was to investigate if SNPs in serotonin and nitric oxide are associated with dengue severity. A retrospective case-control study was conducted, with groups of dengue fever (DF; n = 78) and dengue hemorrhagic fever patients (DHF; n = 49). Genotyping was performed using qPCR and PCR. The power of the sample size was calculated by G*power software. The heterozygous SL for 5-HTTLPR SNP was significantly correlated with protection against progression to DHF in the codominant SS/SL/LL (OR = 0.22, 95% CI = 0.06-0.81, p = 0.011) and overdominant models SL vs SS + LL (OR = 0.19, 95% CI = 0.06-0.65, p = 0.003). For the ENOS (rs1799983) SNP, the genotype GT was positively associated with protection for development of the clinical form in DHF compared to dengue fever (OR = 0.39, 95% CI = (0.13-1.14), p = 0.0058) in codominant GG/GT/TT and overdominant model GT vs GG + TT (OR = 0.35, 95% CI = (0.12-1.02), p = 0.04). To our knowledge, this is the first study to identify the association of the serotonin and nitric oxide SNPs with dengue severity.
Asunto(s)
Óxido Nítrico Sintasa de Tipo III/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Dengue Grave/genética , Adolescente , Adulto , Alelos , Brasil , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores Protectores , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Undernutrition in early life (UELife) is a condition associated with greater occurrence of chronic diseases in adulthood. Some studies on this relationship have used short stature as indicator of UELife. However, other non-nutritional factors can also determine short stature. Depending on the severity of UELife, the human body reacts primarily compromising weight and length gain, but prioritizing brain growth, resulting in disproportionate individuals. Based on this premise, this study aimed to validate a new anthropometric indicator of UELife. DESIGN: Using stature and head circumference data from a probabilistic sample of 3,109 women, the Head-to-Height Index was calculated: HHI = (head × 2.898)/height. A HHI >1.028 (75th percentile) was the best cutoff for predicting obesity (best balance between sensitivity/ specificity, largest area under the receiver operating characteristic curve, and highest correlation coefficient) and was used to define the condition of body disproportionality. The strength of associations with several outcomes was tested for both disproportionality and short stature (height ≤25th percentile: 153.1 cm). RESULTS: In adjusted analysis for confounding factors (age, smoking, and education level), the strength of the associations between body disproportionality and the analyzed outcomes was greater than that observed when short stature was used. Respectively, the observed prevalence ratios (95% CI) were (P<0.05 for all comparisons): obesity: 2.61 (2.17-3.15) vs 1.09 (0.92-1.28); abdominal obesity: 2.11 (1.86-2.40) vs 1.42 (1.27- 1.59); high blood pressure: 1.24 (1.02-1.50) vs 0.90 (0.75-1.08); hypercholesterolemia: 2.98 (1.47-6.05) vs 1.65 (0.91-2.99); and hypertriglyceridemia: 1.47 (1.07-2.03) vs 0.91 (0.69-1.21). CONCLUSION: Body disproportionality is a more accurate indicator of UELife than short stature. While short stature may be genetically determined, a high HHI is due to metabolic adaptations to undernutrition in early life.