Anciuc-Crauciuc Mădălina, Crauciuc George-Andrei, Tripon Florin, Simon Marta, Cucerea Manuela Camelia, Bănescu Claudia Violeta
Doctoral School of Medicine, Institution Organizing University Doctoral Studies (IOSUD), George Emil Palade University of Medicine, Pharmacy, Science, and Technology, 540142 Târgu Mureș, Romania.
Genetics Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology, 540142 Târgu Mureș, Romania.
Diagnostics (Basel). 2025 Sep 6;15(17):2259. doi: 10.3390/diagnostics15172259.
Neonatal respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants. Interleukin-10 (IL-10) and endothelial nitric oxide synthase (eNOS, also known as ) regulate inflammation and vascular tone, and genetic variants may influence the risk of RDS. To investigate the association between rs1800872 (c.-149+1984T>G), rs1800896 (c.-149+2474T>C), and rs2070744 (c.-149+1691C>T), rs1799983 (c.894T>G) variants and the risk of RDS in a Romanian cohort of preterm neonates. This case-control study included 340 preterm neonates (113 with RDS, 227 controls) born at <36 weeks of gestation. Genotyping was performed using TaqMan SNP assays. Logistic regression adjusted for gestational age and sex estimated odds ratios (ORs) and 95% confidence intervals (CIs). ROC analyses evaluated predictive performance. No significant differences in genotype or allele distributions were observed between RDS and control groups for any variant. Haplotype analysis also revealed no association with RDS susceptibility or severity. :c.894T>G variant was associated with reduced risk of severe RDS after correction (adjusted = 0.009), though survival analysis showed no significant genotype-specific effects. Epistatic genotype interaction was observed for the T/G + T/C, present only in RDS ( = 0.0026). ROC analysis revealed a clinical prediction of RDS (AUC = 0.996), while the addition of genetic variants improved discrimination for severity (AUC = 0.865; 95% CI: 0.773-0.957) and mortality (AUC = 0.913; 95% CI: 0.791-1.000). and variants were not individually associated with overall RDS susceptibility. The observed epistatic interactions and the potential protective effect of :c.894T>G against severe forms can suggest modulatory roles in disease progression. Larger, ethnically homogeneous cohorts are needed to confirm these findings and assess their potential for informing personalized care for neonates.
新生儿呼吸窘迫综合征（RDS）是早产儿发病和死亡的主要原因。白细胞介素-10（IL-10）和内皮型一氧化氮合酶（eNOS，也称为 ）调节炎症和血管张力，基因变异可能影响RDS的风险。为了研究rs1800872（c.-149+1984T>G）、rs1800896（c.-149+2474T>C）、rs2070744（c.-149+1691C>T）、rs1799983（c.894T>G）变异与罗马尼亚早产儿队列中RDS风险之间的关联。这项病例对照研究纳入了340例孕周<36周出生的早产儿（113例患有RDS，227例为对照）。使用TaqMan SNP分析进行基因分型。经孕周和性别校正的逻辑回归估计比值比（OR）和95%置信区间（CI）。ROC分析评估预测性能。在任何变异的RDS组和对照组之间，未观察到基因型或等位基因分布的显著差异。单倍型分析也显示与RDS易感性或严重程度无关。：c.894T>G变异在校正后与严重RDS风险降低相关（校正后 = 0.009），尽管生存分析显示没有显著的基因型特异性效应。在仅存在于RDS中的T/G + T/C中观察到上位性基因型相互作用（ = 0.0026）。ROC分析显示RDS的临床预测（AUC = 0.996），而添加基因变异可改善对严重程度的辨别力（AUC = 0.865；95% CI：0.773 - 0.957）和死亡率（AUC = 0.913；95% CI：0.791 - 1.000）。 和 变异与总体RDS易感性无个体关联。观察到的上位性相互作用以及：c.894T>G对严重形式的潜在保护作用可能提示其在疾病进展中的调节作用。需要更大的、种族同质的队列来证实这些发现，并评估它们为新生儿个性化护理提供信息的潜力。
