Department of Pediatrics and CHILD Research, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Pediatr Res. 2012 Jan;71(1):107-14. doi: 10.1038/pr.2011.14.
The genetic contribution to the development of bronchopulmonary dysplasia (BPD) in prematurely born infants is substantial, but information related to the specific genes involved is lacking.
Genotype analysis revealed, after multiple comparisons correction, two significant single-nucleotide polymorphism (SNPs), rs3771150 (IL-18RAP) and rs3771171 (IL-18R1), in African Americans (AAs) with BPD (vs. AAs without BPD; q < 0.05). No associations with Caucasian (CA) BPD, AA or CA respiratory distress syndrome (RDS), or prematurity in either AAs or CAs were identified with these SNPs. Respective frequencies were 0.098 and 0.093 in infants without BPD and 0.38 for each SNP in infants with BPD. In the replication set (82 cases; 102 controls), the P values were 0.012 for rs3771150 and 0.07 for rs3771171. Combining P values using Fisher's method, overall P values were 8.31 × 10(-7) for rs3771150 and 6.33 × 10(-6) for rs3771171.
We conclude that IL-18RAP and IL-18R1 SNPs identify AA infants at risk for BPD. These genes may contribute to AA BPD pathogenesis via inflammatory-mediated processes and require further study.
We conducted a case-control SNP association study of candidate genes (n = 601) or 6,324 SNPs in 1,091 prematurely born infants with gestational age <35 weeks, with or without neonatal lung disease including BPD. BPD was defined as a need for oxygen at 28 days.
早产儿支气管肺发育不良（BPD）的发生与遗传因素有很大关系，但涉及具体相关基因的信息尚缺乏。
经多重比较校正后，基因型分析在患有 BPD 的非裔美国人（AA）中发现了两个显著的单核苷酸多态性（SNP），rs3771150（IL-18RAP）和 rs3771171（IL-18R1）（与无 BPD 的 AA 相比；q<0.05）。这些 SNP 与白种人（CA）BPD、AA 或 CA 呼吸窘迫综合征（RDS）或 AA 或 CA 早产儿均无关联。在无 BPD 的婴儿中，相应的频率分别为 0.098 和 0.093，在患有 BPD 的婴儿中，每个 SNP 的频率均为 0.38。在验证组（82 例；102 例对照）中，rs3771150 的 P 值为 0.012，rs3771171 的 P 值为 0.07。采用 Fisher 方法合并 P 值，rs3771150 的总体 P 值为 8.31×10(-7)，rs3771171 的总体 P 值为 6.33×10(-6)。
我们得出结论，IL-18RAP 和 IL-18R1 SNP 可识别 AA 中患有 BPD 的高危婴儿。这些基因可能通过炎症介导的过程导致 AA BPD 的发病机制，需要进一步研究。
我们对 1091 名胎龄<35 周的早产儿进行了候选基因（n=601）或 6324 个 SNP 的病例对照 SNP 关联研究，这些婴儿有或没有新生儿肺部疾病，包括 BPD。BPD 定义为 28 天需要吸氧。
