Amatya Shaili, Ye Meixia, Yang Lili, Gandhi Chintan K, Wu Rongling, Nagourney Beth, Floros Joanna
Department of Pediatrics, Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Pennsylvania State University College of Medicine, Hershey, PA, United States.
Center for Computational Biology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
Front Pediatr. 2021 Oct 4;9:682160. doi: 10.3389/fped.2021.682160. eCollection 2021.
Neonatal respiratory distress syndrome (RDS), due to surfactant deficiency in preterm infants, is the most common cause of respiratory morbidity. The surfactant proteins () genetic variants have been well-studied in association with RDS; however, the impact of SNP-SNP (single nucleotide polymorphism) interactions on RDS has not been addressed. Therefore, this study utilizes a newer statistical model to determine the association of single SNP model and SNP-SNP interactions in a two and a three SNP interaction model with RDS susceptibility. This study used available genotype and clinical data in the Floros biobank at Penn State University. The patients consisted of 848 preterm infants, born <36 weeks of gestation, with 477 infants with RDS and 458 infants without RDS. Seventeen well-studied , and SNPs were investigated. Wang's statistical model was employed to test and identify significant associations in a case-control study. Only the rs17886395 (C allele) of the was associated with protection for RDS in a single-SNP model (Odd's Ratio 0.16, 95% CI 0.06-0.43, adjusted = 0.03). The highest number of interactions ( = 27) in the three SNP interactions were among and . The three SNP models showed intergenic and intragenic interactions among all SNPs except . The single SNP model and SNP interactions using the two and three SNP interactions models identified -SNP associations with RDS. However, the large number of significant associations containing and/or SNPs point to the importance of and in RDS susceptibility.
新生儿呼吸窘迫综合征（RDS）是由于早产儿表面活性物质缺乏所致，是呼吸疾病最常见的病因。表面活性蛋白（）基因变异与RDS的相关性已得到充分研究；然而，单核苷酸多态性（SNP）-SNP相互作用对RDS的影响尚未得到探讨。因此，本研究采用一种更新的统计模型来确定单SNP模型以及双SNP和三SNP相互作用模型中SNP-SNP相互作用与RDS易感性之间的关联。本研究使用了宾夕法尼亚州立大学弗洛罗斯生物样本库中的可用基因型和临床数据。患者包括848名孕周小于36周的早产儿，其中477名患有RDS，458名未患RDS。研究了17个经过充分研究的、和SNP。在病例对照研究中采用王的统计模型来检验和识别显著关联。在单SNP模型中，只有的rs17886395（C等位基因）与RDS的保护作用相关（优势比0.16，95%可信区间0.06 - 0.43，校正=0.03）。三SNP相互作用中相互作用数量最多（=27）的是和之间。除了之外，三SNP模型在所有SNP中均显示出基因间和基因内相互作用。使用双SNP和三SNP相互作用模型的单SNP模型和SNP相互作用确定了与RDS相关的SNP关联。然而，大量包含和/或SNP的显著关联表明和在RDS易感性中的重要性。
