Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, 361003, Fujian, China.
Xiamen Key Laboratory of Perinatal-Neonatal Infection, Xiamen, China.
Ital J Pediatr. 2024 Oct 29;50(1):225. doi: 10.1186/s13052-024-01776-w.
To investigate the potential influence of adenosine and dopamine receptor genes polymorphisms in combination with clinical factors on the response of preterm infants to caffeine citrate treatment in apnea of prematurity (AOP).
A prospective nested case-control study enrolled 221 preterm infants with gestational age < 34 weeks. These infants were divided into the response (n = 160) and the non-response groups (n = 61). 22 single-nucleotide polymorphisms in adenosine and dopamine receptor genes were genotyped. The basic characteristics and clinical outcomes of the two groups were compared. Univariate logistic regression analysis was performed to evaluate the differences in genotype distribution between the groups. Multivariable logistic regression analysis was performed to identify independent risk and protective factors and develop a nomogram to predict caffeine citrate response in preterm infants.
Preterm infants in the non-response group had lower gestational age, lower birth weight, longer periods of oxygen supplementation and caffeine citrate use, and higher incidence of patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), neonatal respiratory distress syndrome (NRDS), retinopathy of prematurity (ROP), and brain injury (P < 0.05 for all). The ADORA1 rs10920573, ADORA2B rs2015353, ADORA3 rs10776728, DRD3 rs7625282, and DRD3 rs6280 gene polymorphisms were associated with caffeine citrate response in preterm infants (P < 0.05 for all). The ADORA1 rs10920573 CC (aOR, 3.51; 95% CI, 1.34-9.25) and DRD3 rs6280 CT genotypes (aOR, 3.19; 95% CI, 1.53-6.65) were independent risk factors for non-response, whereas greater gestational age (aOR, 0.631; 95% CI, 0.53-0.75) was an independent protective factor for response. The concordance index of the nomogram was 0.764 (95% CI, 0.687-0.842), and the calibration and decision curve analysis indicated the nomogram had excellent predict performance.
Adenosine receptor gene and dopamine receptor gene polymorphisms influence caffeine citrate treatment response in AOP. By combining genetic and clinical variables, it is possible to predict the response to caffeine citrate treatment in preterm infants.
探讨腺苷和多巴胺受体基因多态性与临床因素联合对早产儿呼吸暂停（AOP）中咖啡因枸橼酸盐治疗反应的潜在影响。
前瞻性巢式病例对照研究纳入 221 例胎龄<34 周的早产儿。将这些婴儿分为反应组（n=160）和无反应组（n=61）。对 22 个腺苷和多巴胺受体基因的单核苷酸多态性进行基因分型。比较两组的基本特征和临床结局。采用单因素逻辑回归分析评估两组间基因型分布的差异。采用多因素逻辑回归分析确定独立的风险和保护因素，并建立预测早产儿咖啡因枸橼酸盐反应的列线图。
无反应组早产儿的胎龄更低、出生体重更低、氧疗和咖啡因枸橼酸盐使用时间更长，且动脉导管未闭（PDA）、支气管肺发育不良（BPD）、新生儿呼吸窘迫综合征（NRDS）、早产儿视网膜病变（ROP）和脑损伤的发生率更高（均 P<0.05）。ADORA1 rs10920573、ADORA2B rs2015353、ADORA3 rs10776728、DRD3 rs7625282 和 DRD3 rs6280 基因多态性与早产儿咖啡因枸橼酸盐反应相关（均 P<0.05）。ADORA1 rs10920573 CC（OR，3.51；95%CI，1.34-9.25）和 DRD3 rs6280 CT 基因型（OR，3.19；95%CI，1.53-6.65）是无反应的独立危险因素，而较大的胎龄（OR，0.631；95%CI，0.53-0.75）是反应的独立保护因素。列线图的一致性指数为 0.764（95%CI，0.687-0.842），校准和决策曲线分析表明该列线图具有出色的预测性能。
腺苷受体基因和多巴胺受体基因多态性影响 AOP 中咖啡因枸橼酸盐的治疗反应。通过结合遗传和临床变量，可以预测早产儿对咖啡因枸橼酸盐治疗的反应。
