Department of Molecular Biology & Biochemistry, Guru Nanak Dev University, Amritsar, India.
Department of Human Genetics, Guru Nanak Dev University, Amritsar, India.
Front Cell Infect Microbiol. 2018 Mar 20;8:65. doi: 10.3389/fcimb.2018.00065. eCollection 2018.
Recurrent Vulvovaginal infections (RVVI) are the commonly reported microbiological syndrome affecting millions of women globally. Various molecules of innate immune system are instrumental in clearance of these microbial pathogens, thus suggested as one of the most important contributing factor in determining the disease outcome. Dendritic cell-associated C-type lectin-1 (Dectin-1) is an important molecule of innate immunity that is primarily known for its role in antifungal defenses. However, role of dectin-1 in recognition of other pathogens is also documented. The intracellular expression of dectin-1 was shown to be up-regulated by Mannose Binding Lectin (MBL)-mediated opsonophagocytosis of pathogens. Dectin-1 is encoded by , postulated to be a candidate gene in modulating risk of developing RVVI. In this study, we identified causal variants using analysis. To assess their impact on susceptibility to RVVI, these causal variants along with serum dectin-1 levels (sDectin-1) were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Enzyme Linked Immnosorbent Assay (ELISA) respectively, under a case-control design. Furthermore, effect of these polymorphisms was also assessed on sMBL levels. analysis revealed 9 putative functional conserved SNPs of . Association analysis revealed a significantly lower risk of developing RVVI and its types in carriers of rs3901533 G allele and its homozygous genotypes ( < 0.05). The heterozygous genotype was associated with significant protection against RVVI ( = 0.004). Haplotypes GGG and GTA showed significant protection against RVVI ( < 0.0001; = 0.0003), Bacterial Vaginosis ( = 0.03; = 0.002), Vulvovaginal Candidiasis ( = 0.03; = 0.01) and Mixed Infections ( = 0.007; = 0.04). Mean sDectin-1 levels were significantly high in RVVI and its types compared to controls ( < 0.05). Further, genotype-phenotype stratification showed significant differences within/between cases groups and controls. The rs3901533 polymorphism was also found to be associated with sMBL levels. The present study contributed novel insights into the role of dectin-1 in RVVI. rs3901533 polymorphism and high sDectin-1 levels along with low sMBL levels were found to be associated with RVVI susceptibility. Thus, screening of women with RVVI for these novel associations may lead to better diagnosis and treatment. Also genotyping method used in this study constitutes a simple and reliable assay, which can be confidently, used as a cheaper alternative for genotyping these variants in clinical settings. Finally, new restorative markers for other infectious diseases might be found by exploring nine functionally identified SNPs.
复发性外阴阴道感染（RVVI）是一种常见的微生物综合征，影响着全球数以百万计的女性。先天免疫系统的各种分子在清除这些微生物病原体方面起着重要作用，因此被认为是决定疾病结局的最重要因素之一。树突状细胞相关 C 型凝集素-1（Dectin-1）是先天免疫的重要分子，主要因其在抗真菌防御中的作用而闻名。然而，Dectin-1 在识别其他病原体中的作用也有记录。已经表明，甘露糖结合凝集素（MBL）介导的病原体调理吞噬作用可上调 Dectin-1 的细胞内表达。Dectin-1 由 编码，推测是调节 RVVI 发病风险的候选基因。在这项研究中，我们使用 分析确定了 因果变异。为了评估它们对 RVVI 易感性的影响，我们使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和酶联免疫吸附测定（ELISA）分别在病例对照设计下，研究了这些因果变异与血清 Dectin-1 水平（sDectin-1）之间的关系。此外，还评估了这些多态性对 sMBL 水平的影响。 分析显示了 中的 9 个假定的功能保守 SNP。关联分析显示，携带 rs3901533 G 等位基因及其纯合基因型的个体发生 RVVI 及其类型的风险显著降低（<0.05）。杂合基因型与 RVVI 的显著保护相关（=0.004）。单倍型 GGG 和 GTA 显示出对 RVVI（<0.0001；=0.0003）、细菌性阴道病（=0.03；=0.02）、外阴阴道念珠菌病（=0.03；=0.01）和混合感染（=0.007；=0.04）的显著保护作用。与对照组相比，RVVI 及其类型的 sDectin-1 水平显著升高（<0.05）。进一步的基因型-表型分层显示，病例组和对照组之间存在显著差异。还发现 rs3901533 多态性与 sMBL 水平相关。本研究为 Dectin-1 在 RVVI 中的作用提供了新的见解。 rs3901533 多态性和高 sDectin-1 水平以及低 sMBL 水平与 RVVI 易感性相关。因此，对 RVVI 女性进行这些新型关联的筛查可能会导致更好的诊断和治疗。此外，本研究中使用的基因分型方法构成了一种简单可靠的检测方法，可以有信心地作为临床环境中这些变体基因分型的更便宜替代方法。最后，通过探索九个功能鉴定的 SNPs，可能会发现其他传染病的新恢复性标志物。
