The association of gene polymorphisms of adenosine and dopamine receptors with the response to caffeine citrate treatment in infants with apnea of prematurity: a prospective nested case-control study.

IF 3.2 3区 医学 Q1 PEDIATRICS Italian Journal of Pediatrics Pub Date : 2024-10-29 DOI:10.1186/s13052-024-01776-w
Jiangbiao Xie, Wei Zhuang, Yao Zhu, Zhi Zheng, Yanru Huang, Simin Ma, Xinzhu Lin
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Abstract

Background: 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).

Methods: 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.

Results: 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 (PFDR < 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.

Conclusions: 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.

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腺苷和多巴胺受体基因多态性与早产儿呼吸暂停婴儿对枸橼酸咖啡因治疗反应的关联:一项前瞻性巢式病例对照研究。
研究背景目的:研究腺苷和多巴胺受体基因多态性与临床因素相结合对早产儿呼吸暂停(AOP)时枸橼酸咖啡因治疗反应的潜在影响:方法:一项前瞻性巢式病例对照研究共纳入221名胎龄早产儿:无反应组的早产儿胎龄更小、出生体重更轻、补充氧气和使用枸橼酸咖啡因的时间更长,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(P FDR均<0.05)。ADORA1 rs10920573 CC(aOR,3.51;95% CI,1.34-9.25)和DRD3 rs6280 CT基因型(aOR,3.19;95% CI,1.53-6.65)是导致无应答的独立风险因素,而较大胎龄(aOR,0.631;95% CI,0.53-0.75)则是导致有应答的独立保护因素。提名图的一致性指数为0.764(95% CI,0.687-0.842),校准和决策曲线分析表明提名图具有极佳的预测性能:结论:腺苷受体基因和多巴胺受体基因多态性影响枸橼酸咖啡因对AOP的治疗反应。通过结合遗传和临床变量,可以预测早产儿对枸橼酸咖啡因治疗的反应。
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来源期刊
CiteScore
6.10
自引率
13.90%
发文量
192
审稿时长
6-12 weeks
期刊介绍: Italian Journal of Pediatrics is an open access peer-reviewed journal that includes all aspects of pediatric medicine. The journal also covers health service and public health research that addresses primary care issues. The journal provides a high-quality forum for pediatricians and other healthcare professionals to report and discuss up-to-the-minute research and expert reviews in the field of pediatric medicine. The journal will continue to develop the range of articles published to enable this invaluable resource to stay at the forefront of the field. Italian Journal of Pediatrics, which commenced in 1975 as Rivista Italiana di Pediatria, provides a high-quality forum for pediatricians and other healthcare professionals to report and discuss up-to-the-minute research and expert reviews in the field of pediatric medicine. The journal will continue to develop the range of articles published to enable this invaluable resource to stay at the forefront of the field.
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