RESUMEN
Background: Host genetic factors play a major role with respect to susceptibility to infections. Many polymorphisms of the Toll-like receptors (TLRs), members of the innate immune response, are directly associated with the clinical outcomes following infection. The 2848 G/A variant (rs352140) of the TLR9 gene is associated with increased TLR9 expression. However, the impact of the genotypes of this SNP on HIV+, HCV+, and HCV+/HIV+ individuals is still debated. Materials and Methods: This study investigated the 2848 G/A polymorphism in HCV infection, HIV infection, and HCV/HIV co-infection in a large sample of Brazilians (n = 1,182). Groups were initially compared without considering stratification by ethnicity and subsequently stratifying individuals between whites and non-whites. Results: Considering non-white individuals, a significant difference between the HIV+/HCV+ group and controls was observed with the GG genotype serving as a protective factor (p = 0.023). Additionally, significant allelic differences were observed between the HCV+ group and controls (p = 0.042); between the HIV+/HCV+ group and controls (p = 0.011); and between the HIV+/HCV+ group and HIV+ individuals (p = 0.047). However, all significant results were lost following adjustment for multiple comparisons (p > 0.05). Conclusion: Although our initial results indicated a potential influence of the rs352140 genotype on host altered susceptibility to viral infections, following correction for multiple comparisions the standard (p < 0.05) for statistical association was lost. This may be due to insufficient sample size as we were examining many different associations. Thus, a larger study is warranted to further pursue this topic.
Asunto(s)
Infecciones por VIH , Hepatitis C , Predisposición Genética a la Enfermedad/genética , Genotipo , Infecciones por VIH/genética , Hepatitis C/complicaciones , Hepatitis C/genética , Humanos , Polimorfismo de Nucleótido Simple/genética , Receptor Toll-Like 9/genéticaRESUMEN
In this study we investigated the impact of rs2596542A/G single nucleotide polymorphism (SNP) in the major histocompatibility complex class I chain-related sequence A (MICA) gene on HCV-induced hepatocellular carcinoma (HCC) susceptibility in a Brazilian population. In total, 252 HCV-infected patients (98 with HCV-induced HCC and 154 non-malignant HCV-induced liver cirrhosis) were enrolled and 98 healthy control subjects (negative anti-HCV). The MICA rs2596542 SNP genotypes were determined by real-time PCR assay. No differences in MICA genotype frequencies between HCV-induced cirrhosis patients and controls were observed. However, genotype frequencies of rs2596542A/G SNP were statistically different between HCV-induced HCC patients and controls (p = 0.048), and also between HCC and HCV-induced cirrhosis patients (p = 0.039). The highest frequency of the rs2596542AA genotype was observed in HCC patients (31.6%) when compared with HCV-induced cirrhosis patients (18.8%) and healthy controls (19.4%). Also, rs2596542AA genotype carriers have an increased risk for HCC when compared to HCV-induced cirrhosis status [odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.06-3.74, p = 0.020)] and healthy individuals (OR = 1.92, 95% CI = 1.00-3.70, p = 0.049). Taken together our study suggest that MICA rs2596542 SNP impacts HCV-induced HCC susceptibility suggesting that genetic variants in MICA are of clinical relevance to hepatocarcinogenesis by impacting host immune response in chronic HCV infection.
Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Hepatitis C Crónica/complicaciones , Antígenos de Histocompatibilidad Clase I/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Anciano , Brasil , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
Although a potential involvement of the CCR5Δ32 variant has already been suggested in relation to susceptibility to hepatitis C virus (HCV) infection, data from the literature is still quite controversial. Thus, our study evaluated the influence of the CCR5Δ32 allele variant in HCV infection, HCV/HIV co-infection, and HCV-related diseases in individuals from southern Brazil. A total of 1352 individuals were included in this study, divided into the following groups: Control (nâ¯=â¯274); HCV+ (nâ¯=â¯674); HIV+ (nâ¯=â¯300); HCV+/HIV+ (nâ¯=â¯104). Individuals from the HCV+ group were further stratified according to clinical/histological criteria, as HCV+/control (nâ¯=â¯124); HCV+/fibrosis (nâ¯=â¯268); HCV+/cirrhosis (nâ¯=â¯190); HCV+/hepatocarcinoma (nâ¯=â¯92). Considering all individuals included in this study, the following genotype frequencies were observed: wild-type homozygous (wt/wt), 88.76%; heterozygous (wt/Δ32), 10.72%; variant homozygous (Δ32/Δ32), 0.52%. Genotypic frequencies were very similar between the groups. Of note, the frequency of the Δ32 homozygous was quite similar comparing control uninfected against the HCV+ individuals (pâ¯>â¯0.999). The overall Δ32 allele frequency was estimated at 5.88%. Considering the number of Δ32 allele carriers and non-carriers, no statistically significant differences (pâ¯>â¯0.05) between the groups were observed, suggesting that the CCR5Δ32 variant does not influence the susceptibility to HCV infection, HCV/HIV co-infection, or HCV-related diseases in individuals from southern Brazil.