AUTHOR=Xie Jiang-Biao , Zhuang Wei , Zhu Yao , Zheng Zhi , Huang Yan-Ru , Ma Si-Min , Lin Xin-Zhu 

TITLE=Association between PER and CRY gene polymorphisms and the response to caffeine citrate treatment in infants with apnea of prematurity

JOURNAL=Frontiers in Pediatrics

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2024.1414185

DOI=10.3389/fped.2024.1414185

ISSN=2296-2360

ABSTRACT=<sec><title>Background</title><p>Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between <italic>PER</italic> and <italic>CRY</italic> polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity.</p></sec><sec><title>Methods</title><p>A total of 221 preterm infants of gestational age &lt;34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors <italic>PER</italic> and <italic>CRY</italic> and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the <italic>PER</italic> and <italic>CRY</italic> genes.</p></sec><sec><title>Results</title><p>After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (<italic>P </italic>&gt; 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (<italic>P </italic>= 0.043), retinopathy of prematurity (ROP) (<italic>P </italic>= 0.035), and invasive ventilation (<italic>P </italic>= 0.027), and their duration of oxygen use (<italic>P </italic>= 0.041) was longer. When corrected for false discovery rate, the <italic>PER3</italic> rs228669 recessive model (<italic>P</italic><sub>FDR</sub><italic><sub> </sub></italic>= 0.045) and the over-dominant model (<italic>P</italic><sub>FDR</sub> = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12–0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64–10.66). GMDR analysis revealed an interaction between the <italic>PER</italic> and <italic>CRY</italic> genes (<italic>P </italic>&lt; 0.05).</p></sec><sec><title>Conclusions</title><p>Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the <italic>PER</italic> and <italic>CRY</italic> genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.</p></sec>