Non-HLA gene polymorphisms and their implications on dengue virus infection

Exposure to the dengue virus CDENV [evokes a variety of genetically controlled immunological vesporses. Geneti c variants involued in viral enry, replication and innate immunity path wasys play an important role in the causal pathway of dengue hemorrhagic fever/ dengue shoch syndrome DHF/DSS]. Here we have reviewed implications of some genetic polymorphisms of the pathways related to DENV infection susceptibility, protection and severity. Large case-control studies examining a variety of single-nucleotide polymorphisms [SNPs] in a variety of genes have been performed in DENY patients in some countries. SNP gene candidates that have shown associations with DENV infection are mannose-binding lectin [MBL], interleukin [IL]-4, IL-6, IL-10, interleukin-1 receptor antagonist [IL-1RA], toll-like receptor 4 [TLR4], cytotoxic T-lymphocyte antigen 4 [CTLA-4], tumor necrosis factor [TNF]-alpha, transforming growth factor [TGF]-beta1, Fc gamma receptor II [FcgammaRII], vitamin D receptor [VDR], interferon [IFN]-gamma, human platelet antigens [HPA], transporters associated with antigen processing [TAP], dendritic cell-specific ICAM3-grabbing non-integrin [DC-SIGN] and Janus kinase 1 [JAK1], although some of these genes failed to show statistical significance. Briefly, polymorphism in TNF-alpha, Fc gamma RII, CTLA-4, TGF-beta1, HPA, DC-SIGN, TAP and JAK1 genes has been associated with DHF/DSS development. Polymorphism in MBL2 gene was shown to be associated with thrombocytopenia and increased risk of DHF development. In contrary, polymorphism in VDR gene shows moderate associations with resistance to the most severe form of DHF. However, neutral associations have been reported for IL-4 promoters, IL-1RA, IFN-gamma, IL-6, TLR4 and IL-10 gene polymorphism. In conclusion, there are strong evidences from several epidemiological studies indicating host genetic factors as important components in DENV infection susceptibility, protection and severity

[Effect of nicotine on sperm of normospermic men: modulations made by antioxidants]

Nicotine is one of the major components of cigarette smoke, which have harmful effects like tobacco in human body. Aim of this study is to determine the effect of nicotine on sperm cells. For this purpose we studied the effect of 0.5 and 1mM of nicotine on extent of lipoperoxidation [LPO], balance between oxidized [GSSG] and reduced glutathione [GSH], glutathione S-transferase [GST] activity, and extent of DNA fragmentation with antioxidant interactions in spermatozoa of normospermic men. Vitamin C, glutathione [GSH], and trolox [a water-soluble analog of Vitamin E] were used as antioxidants. Nicotine treatments [0.5 and 1mM] could elevate the level of thiobarbituric acid reactive substances [TBARS] by 51.50% and 78% [P < 0.01 and P < 0.001]. Antioxidants could diminish the TBARS level, amongst trolox was shown better result, but Vitamin C acted as a pro-oxidant when ferrous ions were added to the medium. It was found that the glutathione redox ratio [GSH/GSSG] decreased upon nicotine additions by 49.20% and 60.30% [P < 0.01]. The GST activity also was increased by about 34.01% and 57.19%, in a significant manner respectively. The comet assay results revealed that nicotine could induce severe double-stranded breaks in sperm DNA ladder. Elevated level of TBARS and decreased GSH/GSSG demonstrated a severe peroxidation on sperm membrane lipids through oxygen-derived free radicals. The upgraded activity of GST is an indicator of propagation of LPO in sperm. Collectively, these changes are able to cause inactivation in sperm leading to infertility