RESUMEN
No data exist to assess certain polymorphisms that have a potential effect on the immune response in patients with chronic hepatitis delta (CHD). The aim of this study was to investigate polymorphisms in 6 polymorphic sites: IL-10 -1082 (rs1800896), IL-10 -627 (rs1800872), IFN-γ +874 (rs62559044), TNF-α -308 (rs1800629), vitamin D receptor (VDR) FokI (rs2228570) and VDR TaqI (rs731236). The genotypes of 67 patients with CHD and 119 patients with chronic hepatitis B (CHB) were compared. In addition, 56 individuals with resolved hepatitis B virus (HBV) infection were used as a control group for patients with CHB. Polymorphisms in TNF-α, IL-10, and VDR genes were analysed using polymerase chain reaction/restriction fragment length polymorphism methods. The IFN-γ gene polymorphism was detected by allele-specific polymerase chain reaction (PCR). Patients with CDH were more likely to have advanced liver disease compared with patients with CHB (P < 0.0001). IL-10 -1082 and VDR TaqI polymorphisms showed significant differences between patients with CHD and CHB. The high secretory IL-10 -1082 genotype GG was less frequent in CHD compared with patients with CHB and resolved HBV (17.7%, 37.4% and 47.1%, respectively (P < 0.05 for CHD vs CHB and resolved HBV). The frequency of the high secretory VDR TaqI TT genotype was 86.6% in patients with CHD, 62.7% in patients with CHB and 62.5% in resolved HBV individuals (CHD vs CHB: P < 0.05). None of the polymorphisms analysed had an effect on HBV persistence. IL-10 -1082 and VDR TaqI polymorphisms may contribute to the more severe liver disease associated with CHD compared with CHB.
Asunto(s)
Hepatitis D Crónica/genética , Virus de la Hepatitis Delta/fisiología , Interferón gamma/genética , Interleucina-10/genética , Receptores de Calcitriol/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Alelos , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/genética , Hepatitis B Crónica/virología , Hepatitis D Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Turquía , Carga ViralRESUMEN
The PTPN22 C1858T gene polymorphism has been recently reported to be associated with rheumatoid arthritis (RA) in European and North American ancestry. In contrast, the frequency of PTPN22 C1858T polymorphism is extremely rare in Asian and African populations. As the genetic heterogeneity between populations is clearly present in RA, we wanted to investigate whether the PTPN22 C1858T polymorphism is associated with RA in Turkey and with autoantibody positivity. A total of 323 RA patients and 426 healthy controls were genotyped by polymerase chain reaction restriction fragment length polymorphism for the PTPN22 C1858T polymorphism (rs2476601). The frequencies of heterozygote genotype (CT) were 8.4% in RA patients and 5.4% in the healthy controls, respectively [odds ratio (OR): 1.6, P = 0.14]. The homozygote genotype (T/T) was absent in both RA patients and the healthy controls. When compared with the healthy controls, we found the significant associations between the frequency of PTPN22 heterozygote (CT) polymorphism and RA patients with RF positivity and anti-CCP positivity, respectively (OR: 2.05, P = 0.04 and OR: 2.1, P = 0.03, respectively). Our study suggests that the PTPN22 C1858T polymorphism acts as a susceptibility gene for autoantibody-positive RA in Turkey.
Asunto(s)
Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Autoanticuerpos/sangre , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 22/inmunología , Adulto , Anciano , Artritis Reumatoide/sangre , Artritis Reumatoide/epidemiología , Autoanticuerpos/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/sangre , Estudios Seroepidemiológicos , Turquía/epidemiologíaRESUMEN
In this study, the effect of RNAi on HBV replication was observed in a cell culture model, HepG2 2.2.15 cell line, which supports human HBV ayw replication and expression. Aim of the study was to investigate effects of shRNAs (small hairpin RNAs) targeting hepatitis B virus mRNAs on the viral replication in HepG2 2.2.15 cells. We selected three target HBV mRNA regions with different putative secondary structures to test whether the secondary structure of RNA may affect the inhibition efficacy on the target HBV RNA. Three HBV-specific siRNAs (small interfering RNA) were designed targeting X (1689-1708), Core (2229-2248) and S (765-784 nt) transcripts. HepG2 2.2.15 cells were transfected with shRNA expressing plasmids, P765, P2229 and P1689 targeting S, core and X region, respectively or a mock plasmid targeting lacZ gene. The culture media was collected throughout six days after transfection and analyzed by real-time PCR. Viral DNA production was suppressed for 7 days. The HBV DNA levels were decreased by 73, 72 and 79% with P765, P2229 and P1689 vectors, respectively. In conclusion, the shRNAs designed for X, core and S regions, specifically and significantly suppressed HBV DNA. siRNAs potentially may be used in treatment of hepatitis B.