Genome-wide association study of bronchopulmonary dysplasia: a potential role for variants near the CRP gene.

Bronchopulmonary dysplasia (BPD), the main consequence of prematurity, has a significant heritability, but little is known about predisposing genes. The aim of this study was to identify gene loci predisposing infants to BPD. The initial genome-wide association study (GWAS) included 174 Finnish preterm infants of gestational age 24-30 weeks. Thereafter, the most promising single-nucleotide polymorphisms (SNPs) associated with BPD were genotyped in both Finnish (n = 555) and non-Finnish (n = 388) replication cohorts. Finally, plasma CRP levels from the first week of life and the risk of BPD were assessed. SNP rs11265269, flanking the CRP gene, showed the strongest signal in GWAS (odds ratio [OR] 3.2, p = 3.4 × 10-6). This association was nominally replicated in Finnish and French African populations. A number of other SNPs in the CRP region, including rs3093059, had nominal associations with BPD. During the first week of life the elevated plasma levels of CRP predicted the risk of BPD (OR 3.4, p = 2.9 × 10-4) and the SNP rs3093059 associated nominally with plasma CRP levels. Finally, SNP rs11265269 was identified as a risk factor of BPD (OR 1.8, p = 5.3 × 10-5), independently of the robust antenatal risk factors. As such, in BPD, a potential role for variants near CRP gene is proposed.

Inflammatory activity at school age in very low birth weight bronchopulmonary dysplasia survivors.

OBJECTIVE: Airway inflammation is involved in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of the study was to evaluate the inflammatory activity in plasma and exhaled air in very low birth weight (VLBW) BPD survivors at school age. METHODS: Twenty-one 6-14-year-old former VLBW (birth weight ≤1,500 g) children with severe radiographic BPD (radBPD), 19 without radBPD (nonBPD group) and 19 non-asthmatic term controls underwent measurement of eosinophil cationic protein, IL-6, IL-8, adiponectin, adipsin, leptin, and resistin in plasma, leukotriene B4 and 8-isoprostane in exhaled breath condensate, and NO in exhaled breath. Background data were obtained from patient records, clinical examination and parental questionnaire. Both univariate and multivariate models were applied in the statistical analysis. RESULTS: There were no significant differences between the groups in any of the inflammatory markers measured. Five (25%) radBPD and 2 (11%) nonBPD children reported asthma (P = 0.058). In logistic regression analysis, exposure to chorioamnionitis was associated with low IL-8 (OR 29.0, 95% CI 3.27-258) and postnatal corticosteroid therapy with high adiponectin (OR 32.0, 95% CI 1.29-793). High body mass index standard deviation score (BMI-SDS) was associated with high plasma adipsin (OR 2.47, 95% CI 1.07-5.75) and leptin (OR 5.76, 95%CI 1.83-18.2) levels. CONCLUSIONS: The inflammatory activity seems to decrease by school age in VLBW BPD survivors. Chorioamnionitis and postnatal corticosteroid treatment may modulate the inflammatory responsiveness in VLBW subjects even up to school age. The respiratory outcome in VLBW infants might be improved by preventing excessive weight gain.