Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
J Gene Med. 2017 Aug;19(8). doi: 10.1002/jgm.2971.
Toll like receptors (TLRs) are pattern recognition receptors that recognize molecular patterns of pathogens and play an important role in innate immunity. Recent studies have identified that a single nucleotide polymorphism (SNP) in the TLR gene impairs the response to TLR ligands in some individuals and is associated with susceptibility to various infectious diseases. The present study aimed to investigate the role of four SNPs in the TLR2 gene [-196 to -174 Ins/Del, 2258 G/A (Arg753Gln), 2029 C/T (Arg677Trp) and 1892 C/A (Pro631His)] with respect to susceptibility and progression to HIV-1 in North Indian individuals.
The study population consisted of 160 HIV-1 seropositive patients stratified on the basis of disease severity (stages I, II and III) and 270 HIV-1 seronegative individuals. The subjects were genotyped for TLR2 gene polymorphism by polymerase chain reaction restriction fragment length polymorphism.
In the present study, we found that the TLR2 Del mutant genotype [odds ratio (OR) = 2.138; p = 0.001] and allele (OR = 1.562; p = 0.002) was at a higher frequency in patients with HIV-1 infection compared to healthy controls and was significantly associated with the risk of HIV-1 infection and disease susceptibility. Furthermore, we also found that TLR2 Del homozygous genotype was at a lower frequency in stage III (19.35%) compared to stage I (50.87%; OR = 1.901) and stage II (43.05%; OR = 1.514) and was associated with a reduced risk of HIV-1 disease progression.
The present study reports for the first time that the TLR2-196 to -174 Ins/Del polymorphism is a risk factor for HIV-1 transmission in HIV-1 infected North Indian individuals.
Toll 样受体 (TLR) 是识别病原体分子模式的模式识别受体,在先天免疫中发挥重要作用。最近的研究表明,TLR 基因中的单核苷酸多态性 (SNP) 会损害某些个体对 TLR 配体的反应,并且与各种传染病的易感性相关。本研究旨在探讨 TLR2 基因中的四个 SNP(-196 到 -174Ins/Del、2258G/A(Arg753Gln)、2029C/T(Arg677Trp)和 1892C/A(Pro631His))与印度北部个体 HIV-1 易感性和进展的关系。
研究人群包括根据疾病严重程度(I、II 和 III 期)分层的 160 名 HIV-1 血清阳性患者和 270 名 HIV-1 血清阴性个体。通过聚合酶链反应限制性片段长度多态性对 TLR2 基因多态性进行基因分型。
本研究发现,与健康对照组相比,HIV-1 感染患者中 TLR2 Del 突变基因型(优势比 [OR] = 2.138;p = 0.001)和等位基因(OR = 1.562;p = 0.002)的频率更高,并且与 HIV-1 感染和疾病易感性的风险显著相关。此外,我们还发现,与 I 期(50.87%;OR = 1.901)和 II 期(43.05%;OR = 1.514)相比,III 期 HIV-1 患者 TLR2 Del 纯合基因型的频率较低,与 HIV-1 疾病进展的风险降低相关。
本研究首次报道 TLR2-196 到 -174Ins/Del 多态性是印度北部 HIV-1 感染者 HIV-1 传播的危险因素。