Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Łódź, Poland.
Department of Newborns' Infectious Diseases, Poznań University of Medical Sciences, Poznań, Poland.
Front Immunol. 2021 Oct 28;12:741140. doi: 10.3389/fimmu.2021.741140. eCollection 2021.
Ficolin-2 is regarded as an important innate immunity factor endowed with both lectin (carbohydrate recognition) qualities and ability to induce complement activation. The aim of this study was to investigate the association of the 3'-untranslated region (3'UTR) polymorphisms with ficolin-2 expression and perinatal complications in preterm neonates. The sequencing analysis allowed us to identify six 3'UTR polymorphisms with minor allele frequency (MAF) >1%: rs4521835, rs73664188, rs11103564, rs11103565, rs6537958 and rs6537959. Except for rs4521835, all adhered to Hardy-Weinberg expectations. Moreover, rs6537958 and rs6537959 were shown to be in perfect linkage disequilibrium (LD) with nine other genetic polymorphisms: rs7040372, rs7046516, rs747422, rs7847431, rs6537957, rs6537960, rs6537962, rs11462298 and rs7860507 together stretched on a distance of 1242 bp and very high LD with rs11103565. The 3'UTR region was shown to bind nuclear extract proteins. The polymorphisms at rs4521835 and rs73664188 were found to influence serum ficolin-2 concentration significantly. All polymorphisms identified create (together with exon 8 polymorphism, rs7851696) two haplotype blocks. Among 49 diplotypes (D1-D49) created from rs7851696 (G>T), rs4521835 (T>G), rs73664188 (T>C), rs11103564 (T>C), rs11103565 (G>A) and rs6537959 (T>A), twenty two occurred with frequency >1%. Two diplotypes: D13 (GTTTGT/GGTCGT) and D10 (GTTTGT/GGTCGA), were significantly more frequent among preterm neonates with early onset of infection and pneumonia, compared with newborns with no infectious complications (OR 2.69 and 2.81, respectively; both p<0.05). The minor (C) allele at rs73664188 was associated with an increased risk of very low (≤1500 g) birthweight (OR=1.95, p=0.042) but was associated with the opposite effect at rs11103564 (OR=0.11, p=0.005).
纤维胶凝素-2 被认为是一种重要的先天免疫因子，具有凝集素（碳水化合物识别）特性和诱导补体激活的能力。本研究旨在探讨 3'-非翻译区（3'UTR）多态性与纤维胶凝素-2 表达和早产儿围产期并发症的关系。测序分析允许我们识别出六个 MAF>1%的 3'UTR 多态性：rs4521835、rs73664188、rs11103564、rs11103565、rs6537958 和 rs6537959。除 rs4521835 外，所有多态性均符合 Hardy-Weinberg 预期。此外，rs6537958 和 rs6537959 与其他九个遗传多态性呈完美连锁不平衡（LD）：rs7040372、rs7046516、rs747422、rs7847431、rs6537957、rs6537960、rs6537962、rs11462298 和 rs7860507 一起位于 1242bp 的距离内，与 rs11103565 高度 LD。3'UTR 区域被证明能与核提取物蛋白结合。rs4521835 和 rs73664188 的多态性被发现显著影响血清纤维胶凝素-2 浓度。所有鉴定的多态性与外显子 8 多态性 rs7851696 一起创建了两个单倍型块。从 rs7851696（G>T）、rs4521835（T>G）、rs73664188（T>C）、rs11103564（T>C）、rs11103565（G>A）和 rs6537959（T>A）创建的 49 个单体型（D1-D49）中，有 22 个出现频率>1%。两个单体型：D13（GTTTGT/GGTCGT）和 D10（GTTTGT/GGTCGA），在早发型感染和肺炎的早产儿中明显更频繁，与无感染并发症的新生儿相比（OR 分别为 2.69 和 2.81，均 p<0.05）。rs73664188 的较小（C）等位基因与极低出生体重（≤1500g）的风险增加相关（OR=1.95，p=0.042），但与 rs11103564 的相反效果相关（OR=0.11，p=0.005）。
