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

Autor: Mahlman M; PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland. mari.mahlman@gmail.com.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland. mari.mahlman@gmail.com., Karjalainen MK; PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland., Huusko JM; PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.; Perinatal Institute, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Andersson S; Children's Hospital, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland., Kari MA; Children's Hospital, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland., Tammela OKT; Tampere University Hospital, Tampere University, and Center of Pediatric Child Health, Tampere, Finland., Sankilampi U; Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland., Lehtonen L; Turku University Hospital, and the University of Turku, Turku, Finland., Marttila RH; PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland., Bassler D; Department of Neonatology, University Hospital Zurich, and University of Zurich, Zurich, Switzerland., Poets CF; Department of Neonatology, Tuebingen University Hospital, Tuebingen, Germany., Lacaze-Masmonteil T; Department of Paediatrics, Cumming School of Medicine, University of Calgary, Alberta, Canada., Danan C; Inserm, U955, Créteil, France.; CRB, CHI-Creteil, France.; Department of neonatology, CHI-Creteil, Creteil, France., Delacourt C; Inserm, U955, Créteil, France.; AP-HP, Hôpital Necker-Enfants Malades, Service de Pneumologie Pédiatrique, Paris, France.; Université Paris-Descartes, Paris, France., Palotie A; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.; Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA., Muglia LJ; Perinatal Institute, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Lavoie PM; BC Children's Hospital Research Institute, Vancouver Canada, Vancouver, Canada., Hadchouel A; Inserm, U955, Créteil, France.; AP-HP, Hôpital Necker-Enfants Malades, Service de Pneumologie Pédiatrique, Paris, France.; Université Paris-Descartes, Paris, France., Rämet M; PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.; BioMediTech Institute and Faculty of Medical and Life Sciences, University of Tampere, Tampere, Finland., Hallman M; PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Aug 24; Vol. 7 (1), pp. 9271. Date of Electronic Publication: 2017 Aug 24.
DOI: 10.1038/s41598-017-08977-w
Abstrakt: 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.
Databáze: MEDLINE