Association of vitamin D receptor gene polymorphisms and bronchopulmonary dysplasia

Köroğlu, Özge Altun; Önay, Hüseyin; Çakmak, Bülent; Bilgin, Betül Siyah; Yalaz, Mehmet; Tunc, Seckin; Özkınay, Ferda; Kültürsay, Nilgün

doi:10.1038/pr.2014.63

Cited by 35 publications

(16 citation statements)

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“…40 In a very recent study, VDR Fok 1 polymorphism was found to be associated with increased frequency of BPD. 41 Our study is the first in the literature to demonstrate a possible association between maternal/neonatal 25-OHD levels and BPD. We found that every 1 ng ml − 1 increase in vitamin D level of the mother and the newborn decreased the probability of BPD by 24% and 39%, respectively, showing that vitamin D level of the mother and the newborn was a significant predictor of BPD.…”

Section: Discussionmentioning

confidence: 59%

Maternal/neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms?

et al. 2015

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Section: Discussionmentioning

confidence: 59%

Maternal/neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms?

et al. 2015

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“…The other identified observational study (50) concluded that the VDR Fok I polymorphism was associated with an increased adjusted risk of BPD. However, the association was not detectable when controlling for the very important confounders, gestational age and birth weight.…”

Section: Discussionmentioning

confidence: 99%

The impact of vitamin D on fetal and neonatal lung maturation. A systematic review

Lykkedegn

Sørensen

Beck-Nielsen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

122

104

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-Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) are major complications to preterm birth. Hypovitaminosis D is prevalent in pregnancy. We systematically reviewed the evidence of the impact of vitamin D on lung development, surfactant synthesis, RDS, and BPD searching PubMed, Embase, and Cochrane databases with the terms vitamin D AND (surfactant OR lung maturation OR lung development OR respiratory distress syndrome OR fetal lung OR prematurity OR bronchopulmonary dysplasia). Three human studies, ten animal studies, two laboratory studies, and one combined animal and laboratory study were included. Human evidence was sparse, allowing no conclusions. BPD was not associated with vitamin D receptor polymorphism in a fully adjusted analysis. Animal and laboratory studies showed substantial positive effects of vitamin D on the alveolar type II cell, fibroblast proliferation, surfactant synthesis, and alveolarization. These data support the hypothesis of hypovitaminosis D as a frequent, modifiable risk factor of RDS and BPD, which should be tested in randomized controlled trials on pregnant women, those with threatening preterm delivery, or in the preterm neonates. Future experimental and human studies should aim to identify optimal time windows, vitamin D doses, and cut-off levels for 25-hydroxyvitamin D in interventions against RDS, BPD, and later adverse respiratory outcomes. vitamin D; fetus; lung; surfactant; preterm; neonate THE IMPORTANCE OF VITAMIN D in nonskeletal fetal and childhood health has become increasingly recognized in the last decades (19,65). The impact of vitamin D on early lung development and maturation and lung diseases of early life is an emerging field of research. Hypovitaminosis D during pregnancy is associated with reduced placental development and weight, leading to a presumed risk of preterm birth (24,25), which per se may lead to respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). Moreover, vitamin D is suggested to play a role in the embryogenesis and in cellular growth and differentiation, including lung development and regulation of lung maturation in the fetus (23,29,38,70,71,108), whereby hypovitaminosis D could be hypothesized to aggravate premature neonatal lung diseases.Vitamin D is involved in the development of the innate and adaptive immune system, and, because of its unique capacity to bind to the vitamin D receptor (VDR) and thereby to serve as a transcriptional factor, vitamin D can regulate gene expression and exert widespread immunomodulatory effects including proliferation, differentiation, and complex regulation (19, 56, 58 -61, 64, 65, 68, 69, 105). Evidence suggests that vitamin D may stimulate regulatory T cell development and T cell function to suppress inappropriate Th1 and Th2 responses to environmental exposure (i.e., allergens, infection load), leading to a more balanced immune response inhibiting autoimmune diseases (with Th1 dominance) and allergic diseases (Th2 dominance) (55). Vitamin D could therefore be inv...

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“…However, genome-wide association studies have been variably successful [65, 66] and unsuccessful [67] in identifying candidate single nucleotide polymorphisms associated with BPD. Polymorphisms in the vitamin D receptor gene were recently shown to be associated with BPD in preterm newborns supporting preclinical studies in which vitamin D augments angiogenesis both in vitro and in LPS-induced experimental BPD [68, 69]. …”

Section: Introductionmentioning

confidence: 88%

Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia

Baker

Abman²

2015

Neonatology

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Bronchopulmonary dysplasia (BPD), the chronic lung disease associated with preterm birth, results from the disruption of normal pulmonary vascular and alveolar growth. Though BPD was once described as primarily due to postnatal injury from mechanical ventilation and oxygen therapy after preterm birth, it is increasingly appreciated that BPD results from antenatal and perinatal factors that interrupt lung development in infants born at the extremes of prematurity. The lung in BPD consists of a simplified parenchymal architecture that limits gas exchange and leads to increased cardiopulmonary morbidity and mortality. This review outlines recent advances in the understanding of pulmonary vascular development and describes how the disruption of these mechanisms results in BPD. We point to future therapies that may augment postnatal vascular growth to prevent and treat this severe chronic lung disease.

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Association of vitamin D receptor gene polymorphisms and bronchopulmonary dysplasia

Cited by 35 publications

References 35 publications

Maternal/neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms?

Maternal/neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms?

The impact of vitamin D on fetal and neonatal lung maturation. A systematic review

Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia

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