Universität zu Köln

Blume, Felix, Kirsten, Holger ORCID: 0000-0002-3126-7950, Ahnert, Peter ORCID: 0000-0002-1771-0856, Chakraborty, Trinad, Gross, Arnd ORCID: 0000-0002-5961-5507, Horn, Katrin, Toliat, Mohammad Reza, Nurnberg, Peter, Westenfelder, Eva-Maria, Goepel, Wolfgang and Scholz, Markus . Verification of immunology-related genetic associations in BPD supports ABCA3 and five other genes. Pediatr. Res.. LONDON: SPRINGERNATURE. ISSN 1530-0447

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Abstract

Background Inflammatory processes are key drivers of bronchopulmonary dysplasia (BPD), a chronic lung disease in preterm infants. In a large sample, we verify previously reported associations of genetic variants of immunology-related genes with BPD. Methods Preterm infants with a gestational age <= 32 weeks from PROGRESS and the German Neonatal Network (GNN) were included. Through a consensus case/control definition, 278 BPD cases and 670 controls were identified. We identified 49 immunity-related genes and 55 single-nucleotide polymorphisms (SNPs) previously associated with BPD through a comprehensive literature survey. Additionally, a quantitative genetic association analysis regarding oxygen supplements, mechanical ventilation, and continuous positive air pressure (CPAP) was performed. Results Five candidate SNPs were nominally associated with BPD-related phenotypes with effect directions not conflicting the original studies: rs11265269-CRP, rs1427793-NUAK1, rs2229569-SELL, rs1883617-VNN2, and rs4148913-CHST3. Four of these genes are involved in cell adhesion. Extending our analysis to all well-imputed SNPs of all candidate genes, the strongest association was rs45538638-ABCA3 with CPAP (p = 4.9 x 10(-7), FDR = 0.004), an ABC transporter involved in surfactant formation. Conclusions Most of the previously reported associations could not be replicated. We found additional support for SNPs in CRP, NUAK1, SELL, VNN2, and ABCA3. Larger studies and meta-analyses are required to corroborate these findings. Impact Larger cohort for improved statistical power to detect genetic associations with bronchopulmonary dysplasia (BPD). Most of the previously reported genetic associations with BPD could not be replicated in this larger study. Among investigated immunological relevant candidate genes, additional support was found for variants in genes , , , , and , four of them related to cell adhesion. rs45538638 is a novel candidate SNP in reported candidate gene ABC-transporter . Results help to prioritize molecular candidate pathomechanisms in follow-up studies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Blume, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirsten, Holger UNSPECIFIED orcid.org/0000-0002-3126-7950 UNSPECIFIED Ahnert, Peter UNSPECIFIED orcid.org/0000-0002-1771-0856 UNSPECIFIED Chakraborty, Trinad UNSPECIFIED UNSPECIFIED UNSPECIFIED Gross, Arnd UNSPECIFIED orcid.org/0000-0002-5961-5507 UNSPECIFIED Horn, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Toliat, Mohammad Reza UNSPECIFIED UNSPECIFIED UNSPECIFIED Nurnberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Westenfelder, Eva-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Goepel, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholz, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-595212
DOI:	10.1038/s41390-021-01689-y
Journal or Publication Title:	Pediatr. Res.
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1530-0447
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; SURFACTANT PROTEIN-A; BRONCHOPULMONARY DYSPLASIA; RISK-FACTORS; POLYMORPHISMS; SUSCEPTIBILITY; BIRTH; IDENTIFICATION; ANNOTATION; DEFINITION Multiple languages Pediatrics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59521