关键词: dengue innate immunity tlr 9 tlr3 tlr7 toll-like receptors

来  源:   DOI:10.7759/cureus.14883   PDF(Pubmed)

Abstract:
Introduction The endosomal toll-like receptors (TLR) TLR3, TLR7, and TLR9 are localized in immune cells, recognize the viral pattern associated molecular pattern (PAMPs), and start signaling cascades for immune defense response and genetic factor is known to affect the dengue virus infection therefore in our study we study the association of endosomal Toll-like receptors 3 polymorphism rs3775291, rs3775290, and rs3775296 with rs179008 A/T and rs179009C/T polymorphisms of TLR7 and rs187084 (C/T), rs5743836 (C/T) of TLR9 gene with dengue and controls. Materials and methods Ninety-eight cases of dengue virus (DV) infection and 98 healthy controls were enrolled. Clinical details were recorded and cases were classified as severe or non-severe dengue, based on WHO 2009 classification. Genotypes were determined by Sanger sequencing using the genetic analyzer. Results An increased risk of DV infection was observed in cases as compared to controls, with TLR 3 rs3775291 CT genotype (OR = 4.34, P-value: 0.031, CI = 1.14-16.5), Likewise in TLR7 rs179008 AT (OR = 2.12, P-value: 0.034, CI = 1.06-4.26) and rs179009 CT (OR = 2.04, P-value: 0.040, CI = 1.03-4.05) same as in TLR9 rs187084 CT (OR = 1.97, P-value: 0.046, CI = 1.013-3.84) and rs5743836 (OR = 2.38, P-value: 0.009, CI = 1.24-5.57). In the above polymorphisms, mutant allele was observed in a significantly higher number in cases. The values are: for TLR3 rs3775291 T allele (OR 2.167, CI = 1.3-3.61, P-value: 0.003). TLR7 rs179008 T allele (OR 1.90, P-value: 0.021, CI = 1.07-3.35) and in TLR9 rs187084 (OR 1.91, P-value: 0.014, CI = 1.137-3.24) rs5743836 (OR 2.29, P-value: 0.0018, CI = 1.36-3.87). No significant association was observed in the genotypic frequency of severe versus non-severe dengue. Conclusion TLR3, 7, and 9 gene polymorphism might confer host genetic susceptibility to dengue in the North Indian population.
摘要:
介绍内体toll样受体(TLR)TLR3,TLR7和TLR9位于免疫细胞中,识别病毒模式相关分子模式(PAMPs),并且启动免疫防御反应的信号传导级联,遗传因素已知会影响登革热病毒感染,因此在我们的研究中,我们研究了内体Toll样受体3多态性rs3775291,rs3775290和rs3775296与rs179008A/T和rs179009C/T的相关性TLR7和rs187084(C/T)的多态性,TLR9基因rs5743836(C/T)与登革热和对照。材料与方法选择98例登革病毒(DV)感染病例和98例健康对照者。记录临床细节,并将病例分为严重或非严重登革热,根据世卫组织2009年的分类。使用遗传分析仪通过Sanger测序确定基因型。结果与对照组相比,在病例中观察到DV感染的风险增加。TLR3rs3775291CT基因型(OR=4.34,P值:0.031,CI=1.14-16.5),TLR7rs179008AT(OR=2.12,P值:0.034,CI=1.06-4.26)和rs179009CT(OR=2.04,P值:0.040,CI=1.03-4.05)与TLR9rs187084CT(OR=1.97,P值:0.046,CI=1.013-3.84)和rs57436(OR=1.38P=2.38,在上述多态性中,在病例中观察到突变等位基因的数量明显更高。值是:对于TLR3rs3775291T等位基因(OR为2.167,CI=1.3-3.61,P值:0.003)。TLR7rs179008T等位基因(OR1.90,P值:0.021,CI=1.07-3.35)和TLR9rs187084(OR1.91,P值:0.014,CI=1.137-3.24)rs5743836(OR2.29,P值:0.0018,CI=1.36-3.87)。在严重与非严重登革热的基因型频率中未观察到显着关联。结论TLR3、7和9基因多态性可能赋予北印度人群宿主登革热遗传易感性。
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