Hilgendorff A, Heidinger K, Pfeiffer A, Bohnert A, König I R, Ziegler A, Merz C, Frey G, Chakraborty T, Gortner L, Bein G
Department of Paediatrics, University of Giessen and Marburg, Giessen, Germany.
Genes Immun. 2007 Dec;8(8):671-7. doi: 10.1038/sj.gene.6364432. Epub 2007 Sep 27.
Deficiency in the collectin mannose-binding lectin (MBL) increases the risk for pulmonary and systemic infections and its complications in children and adults. The aim of this prospective cohort study was to determine the genetic association of sequence variations within the MBL gene with systemic infections and pulmonary short- and long-term complications in preterm infants below 32 weeks gestational age (GA). Three single-nucleotide polymorphisms (SNPs) in the coding region and one SNP in the promotor region of MBL2 were genotyped by direct sequencing and with sequence-specific probes in 284 newborn infants <32 weeks GA. Clinical variables were comprehensively monitored. An association was found between two SNPs and the development of bronchopulmonary dysplasia (BPD), defined as persistent oxygen requirement at 36 weeks postmenstrual age, adjusting for covariates GA, grade of respiratory distress syndrome and days on mechanical ventilation (rs1800450 (exon 1 at codon 54, B variant): odds ratio dominant model (OR)=3.59, 95% confidence interval (CI)=1.62-7.98; rs7096206 (-221, X variant): OR=2.40, 95% CI=1.16-4.96). Haplotype analyses confirmed the association to BPD, and a single haplotype (frequency 56%) including all SNPs in their wild-type form showed a negative association with the development of BPD. We detected no association between the MBL gene variations and the development of early-onset infections or further pulmonary complications. Frequent variants of the MBL gene, leading to low MBL concentrations, are associated with the diagnosis of BPD in preterm infants. This provides a basis for potential therapeutic options and further genetic and proteomic analysis of the function of MBL in the resistance against pulmonary long-term complications in preterm infants.
凝集素甘露糖结合凝集素（MBL）缺乏会增加儿童和成人发生肺部和全身性感染及其并发症的风险。这项前瞻性队列研究的目的是确定MBL基因序列变异与胎龄小于32周的早产儿全身性感染以及肺部短期和长期并发症之间的遗传关联。通过直接测序和序列特异性探针，对284名胎龄小于32周的新生儿的MBL2编码区的三个单核苷酸多态性（SNP）和启动子区的一个SNP进行基因分型。对临床变量进行了全面监测。在调整了协变量胎龄、呼吸窘迫综合征分级和机械通气天数后，发现两个SNP与支气管肺发育不良（BPD）的发生有关，BPD定义为月经龄36周时持续需要吸氧（rs1800450（第1外显子第54密码子，B变异）：显性模型优势比（OR）=3.59，95%置信区间（CI）=a1.62 - 7.98；rs7096206（-221，X变异）：OR = 2.40，95% CI = 1.16 - 4.96）。单倍型分析证实了与BPD的关联，一种包含所有野生型形式SNP的单倍型（频率56%）与BPD的发生呈负相关。我们未检测到MBL基因变异与早发性感染或其他肺部并发症的发生之间存在关联。导致MBL浓度降低的MBL基因常见变异与早产儿BPD的诊断有关。这为潜在的治疗选择以及进一步对MBL在抵抗早产儿肺部长期并发症中的功能进行基因和蛋白质组学分析提供了依据。
