Mikolajcikova Silvia, Lasabova Zora, Holubekova Veronika, Skerenova Maria, Zibolenova Jana, Matasova Katarina, Zibolen Mirko, Calkovska Andrea
Clinic of Neonatology, Jessenius Faculty of Medicine, Comenius University and University Hospital, Martin, Slovakia.
Department of Molecular Biology and Genomics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
Front Pediatr. 2022 May 25;10:851042. doi: 10.3389/fped.2022.851042. eCollection 2022.
Respiratory distress syndrome (RDS), a disorder of primary surfactant deficiency resulting in pulmonary insufficiency, remains a significant problem for preterm neonates. Associations between genetic variants of surfactant proteins and RDS have been reported, but haplotypes of the surfactant protein B gene () have not been studied. The aim of the study was to prove the hypothesis that certain haplotypes of may be protective or risk factors for RDS.
The study was performed with 149 preterm infants, born <34 weeks of gestation, with 86 infants with mild RDS or without RDS (control group) and 63 infants with severe RDS (patient group). RDS was considered severe if multiple doses of exogenous surfactant and/or mechanical ventilation within the first 72 h of life were needed. The venous blood sample was used for the analysis of gene polymorphisms associated with RDS, genotyping, and haplotype estimation. Multivariate logistic regression analysis and the odds ratio were calculated to detect the contribution of the studied variables to the development of RDS.
A new association of the common single nucleotide polymorphism (SNP) rs2304566 with RDS in premature infants was detected. Analysis of rs2304566 polymorphisms using a logistic regression model showed that there are two significant predictors inversely related to the occurrence of RDS (Apgar score of 5 min, CT and TT genotype in rs2304566 polymorphism). Gestational age, birth weight, and sex have border significance. Moreover, in the patient group, the frequency of the GATGACA haplotype in the gene was lower ( = 0.037), and the GATGGCA haplotype was higher ( = 0.059) in comparison with the control group.
The common haplotype GATGACA of the gene can be protective against RDS in preterm infants. The trend of a higher frequency of GATGGCA in the gene in infants with severe RDS suggests that this haplotype may be a risk factor for RDS susceptibility.
呼吸窘迫综合征（RDS）是一种原发性表面活性物质缺乏导致肺功能不全的疾病，仍然是早产新生儿面临的一个重大问题。已有报道表面活性物质蛋白的基因变异与RDS之间存在关联，但表面活性物质蛋白B基因（）的单倍型尚未得到研究。本研究的目的是验证以下假设：特定的单倍型可能是RDS的保护因素或风险因素。
对149例孕周小于34周的早产儿进行研究，其中86例患有轻度RDS或无RDS（对照组），63例患有重度RDS（患者组）。如果在出生后72小时内需要多次使用外源性表面活性物质和/或机械通气，则认为RDS为重度。采集静脉血样本用于分析与RDS相关的基因多态性、基因分型和单倍型估计。计算多因素逻辑回归分析和优势比，以检测所研究变量对RDS发生的影响。
检测到常见单核苷酸多态性（SNP）rs2304566与早产儿RDS之间的新关联。使用逻辑回归模型对rs2304566多态性进行分析表明，有两个与RDS发生呈负相关的显著预测因素（5分钟阿氏评分、rs2304566多态性中的CT和TT基因型）。孕周、出生体重和性别具有临界意义。此外，与对照组相比，患者组中基因的GATGACA单倍型频率较低（=0.037），而GATGGCA单倍型频率较高（=0.059）。
基因的常见单倍型GATGACA可预防早产儿发生RDS。重度RDS婴儿中基因的GATGGCA频率较高的趋势表明，该单倍型可能是RDS易感性的一个风险因素。
