Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Child's Nervous System
Published in: Child's Nervous System 8/2020

Open Access 01-08-2020 | Original Article

Role of Fibronectin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants

Authors: Dawid Szpecht, Salwan R. Al-Saad, Lukasz M. Karbowski, Katarzyna Kosik, Grażyna Kurzawińska, Marta Szymankiewicz, Krzysztof Drews, Agnieszka Seremak-Mrozikiewicz

Published in: Child's Nervous System | Issue 8/2020

Login to get access

Abstract

Background/introduction

Intraventricular hemorrhage (IVH) is a dangerous complication facing a significant proportion of preterm infants. It is multifactorial in nature, and an observed fibronectin deficiency in the germinal matrix basal lamina is among the most prominent factors that influence such rupture. Better understanding of the FN1 gene polymorphisms and their role in IVH may further clarify the presence of a genetic susceptibility of certain babies to this complication. The aim of this study was to assess if 5 single nucleotide polymorphisms of the fibronectin gene may be linked to an increased incidence of IVH.

Material and methods

The study included 108 infants born between 24 and 32 weeks of gestation. IVH was diagnosed using cranial ultrasound performed on the 1st,3rd, and 7th day after birth and classified according to Papile et al. IVH classification. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655.

Results

IVH developed in 51 (47.2%) out of the 108 preterm infants. This includes, 18 (35.3%) with stage I IVH, 19 (37.3%) with stage II, 11 (21.6%) with stage III, and 3 (5.9%) with stage IV IVH. Incidence of IVH was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Analysis showed that IVH stage II to IV was approximately seven times more likely to occur in infants with the genotype TT FN1 rs10202709 (OR 7237 (1046–79.59; p = 0,044)). No other significant association was found with the rest of the polymorphisms.

Conclusion

The results of our study indicate a sevenfold increased genetic susceptibility to IVH in preterm infants with the TT FN1 rs10202709 gene polymorphism. The fibronectin gene polymorphism may therefore be of crucial importance as a genetic risk factor for IVH in preterm infants. Further studies are warranted.
Appendix
Available only for authorised users
Literature
1.
Sherlock R, Anderson P, Doyle L, Callanan C, Carse E, Casalaz D et al (2005) Neurodevelopmental sequelae of intraventricular haemorrhage at 8 years of age in a regional cohort of ELBW/very preterm infants. Early Hum Dev 81(11):909–916CrossRefPubMed
2.
Luu T, Ment L, Schneider K, Katz K, Allan W, Vohr B (2009) Lasting effects of preterm birth and neonatal brain hemorrhage at 12 years of age. Pediatrics 123(3):1037–1044CrossRefPubMedPubMedCentral
3.
Jain N, Kruse L, Demissie K, Khandelwal M (2009) Impact of mode of delivery on neonatal complications: trends between 1997 and 2005. J Matern Fetal Neonatal Med 22(6):491–500CrossRefPubMed
4.
Christian E, Jin D, Attenello F, Wen T, Cen S, Mack W et al (2015) Trends in hospitalization of preterm infants with intraventricular hemorrhage and hydrocephalus in the United States, 2000-2010. Fluids Barriers CNS 12(Suppl 1):O1CrossRefPubMedCentral
5.
Linder N, Haskin O, Levit O, Klinger G, Prince T, Naor N, Turner P, Karmazyn B, Sirota L (2003) Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study. Pediatrics 111(5 Pt 1):e590-5
6.
Ballabh P (2014) Pathogenesis and prevention of Intraventricular hemorrhage. Clin Perinatol 41(1):47–67CrossRefPubMed
7.
Szpecht D, Gadzinowski J, Seremak-Mrozikiewicz A, Kurzawińska G, Drews K, Szymankiewicz M (2017) The significance of polymorphisms in genes encoding Il-1β, Il-6, TNFα, and Il-1RN in the pathogenesis of intraventricular hemorrhage in preterm infants. Childs Nerv Syst 33(11):1905–1916CrossRefPubMedPubMedCentral
8.
Adcock K, Hedberg C, Loggins J, Kruger T, Baier R (2003) The TNF-α −308, MCP-1 -2518 and TGF-β1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants. Genes Immun 4(6):420–426CrossRefPubMed
9.
Petäjä J., Hiltunen L., Fellman V (2001) Increased risk of Intraventricular hemorrhage in preterm infants with thrombophilia
10.
Melegh B, Stankovics J, Kis A, Nagy A, Storez J, Losonczy H, Méhes K (1998) Increased prevalence of factor V Leiden mutation in neonatal intracranial haemorrhage [3]. Eur J Pediatr 157(3):261PubMed
11.
12.
Szpecht D, Gadzinowski J, Seremak-Mrozikiewicz A, Kurzawińska G, Szymankiewicz M (2017) Role of endothelial nitric oxide synthase and endothelin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants. Sci Rep 7
13.
Bilguvar K, DiLuna M, Bizzarro M, Bayri Y, Schneider K, Lifton R, Gunel M, Ment LR, Pacifier and Breastfeeding Trial Group (2009) COL4A1 mutation in preterm Intraventricular hemorrhage. J Pediatr 155(5):743–745CrossRefPubMedPubMedCentral
14.
Ment L, Ådén U, Lin A, Kwon S, Choi M, Hallman M et al (2014) Gene-environment interactions in severe intraventricular hemorrhage of preterm neonates. Pediatr Res 75(1–2):241–250CrossRefPubMed
15.
Raets M, Dudink J, Govaert P (2015) Neonatal disorders of germinal matrix. J Matern Fetal Neonatal Med 28:2286–2290CrossRefPubMed
16.
Kinoshita Y, Okudera T, Tsuru E, Yokota A (2001) Volumetric analysis of the germinal matrix and lateral ventricles performed using MR images of postmortem fetuses
17.
Ballabh P, Braun A, Nedergaard M (2004) Anatomic analysis of blood vessels in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res 56(1):117–124CrossRefPubMed
18.
Ballabh P, Braun A, Nedergaard M (2004) The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16(1):1–13CrossRefPubMed
19.
Persidsky Y, Ramirez S, Haorah J, Kanmogne G (2006) Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J NeuroImmune Pharmacol 1:223–236CrossRefPubMed
20.
Tilling T, Engelbertz C, Decker S, Korte D, Hüwel S, Galla H (2002) Expression and adhesive properties of basement membrane proteins in cerebral capillary endothelial cell cultures. Cell Tissue Res 310(1):19–29CrossRefPubMed
21.
22.
Xu H, Hu F, Sado Y, Ninomiya Y, Borza D, Ungvari Z, Lagamma EF, Csiszar A, Nedergaard M, Ballabh P (2008) Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone. J Neurosci Res 86(7):1482–1500CrossRefPubMed
23.
Mao Y, Schwarzbauer J (2005) Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol 24(6):389–399CrossRefPubMed
24.
25.
Avila J, Lympany P, Pantelidis P, Welsh K, Black C, Du Bois R (1999) Fibronectin gene polymorphisms associated with fibrosing alveolitis in systemic sclerosis
26.
Murat M, Aekeper A, Yuan L, Alim T, Du G, Abdusamat A et al (2015) Correlation between the development of calcium oxalate stones and polymorphisms in the fibronectin gene in the Uighur population of the Xinjiang region of China. Genet Mol Res 14(4):13728–13734CrossRefPubMed
27.
28.
29.
El-Khoury N, Braun A, Hu F, Pandey M, Nedergaard M, Lagamma E, Ballabh P (2006) Astrocyte end-feet in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res 59(5):673–679CrossRefPubMed
30.
Braun A, Xu H, Hu F, Kocherlakota P, Siegel D, Chander P et al (2007) Paucity of pericytes in germinal matrix vasculature of premature infants. J Neurosci 27(44):12012–12024CrossRefPubMedPubMedCentral
31.
Watkins S, Robel S, Kimbrough I, Robert S, Ellis-Davies G, Sontheimer H (2014) Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells. Nat Commun 5
32.
33.
Schreiber S, Bueche C, Garz C, Braun H (2013) Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - new insights from a rat model. Exp Transl Stroke Med 5(1)
34.
Ment L, Ådén U, Bauer C, Bada H, Carlo W, Kaiser J et al (2015) Genes and environment in neonatal intraventricular hemorrhage. Semin Perinatol 39(8):592–603CrossRefPubMedPubMedCentral
35.
Szpecht D, Gadzinowski J, Seremak-Mrozikiewicz A, Kurzawińska G, Drews K, Szymankiewicz M (2017) The role of FV 1691G>A, FII 20210G>A mutations and MTHFR 677C>T; 1298A>C and 103G>T FXIII gene polymorphisms in pathogenesis of intraventricular hemorrhage in infants born before 32 weeks of gestation. Childs Nerv Syst 33(7):1201–1208CrossRefPubMedPubMedCentral
36.
Prasun P, Madan R, Puthuraya S, Subramanian D, Datta I, Kalra V, Thomas R, Stockton DW, Sundaram S, Callaghan J, Callaghan M, Chouthai N (2018) Can functional polymorphisms in VEGF and MMP predict intraventricular hemorrhage in extremely preterm newborns? Dev Neurosci 40(4):337–343CrossRefPubMed
37.
Castelletti F, Donadelli R, Banterla F, Hildebrandt F, Zipfel P, Bresin E et al (2008) Mutations in FN1 cause glomerulopathy with fibronectin deposits
38.
Onaran M, Yilmaz A, Şen I, Ergun M, Çamtosun A, Küpeli B et al (2009) A HindIII polymorphism of Fibronectin gene is associated with nephrolithiasis. Urology 74(5):1004–1007CrossRefPubMed
39.
Lee C, Fu H, Baratang N, Rousseau J, Kumra H, Sutton V, Niceta M, Ciolfi A, Yamamoto G, Bertola D, Marcelis CL, Lugtenberg D, Bartuli A, Kim C, Hoover-Fong J, Sobreira N, Pauli R, Bacino C, Krakow D, Parboosingh J, Yap P, Kariminejad A, McDonald M, Aracena MI, Lausch E, Unger S, Superti-Furga A, Lu JT, Baylor-Hopkins Center for Mendelian Genomics, Cohn DH, Tartaglia M, Lee BH, Reinhardt DP, Campeau PM (2017) Mutations in fibronectin cause a subtype of spondylometaphyseal dysplasia with “corner fractures”. Am J Hum Genet 101(5):815–823CrossRefPubMedPubMedCentral
40.
Yang H, Su S, Peng Y, Wang C, Lee H, Salter D, Lee C (2014) An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population: two independent case - control studies. BMC Musculoskelet Disord 15(1)
41.
Nakata K, Ujike H, Sakai A, Takaki M, Imamura T, Tanaka Y, Kuroda S (2003) Association study between the fibronectin gene and schizophrenia. Am J Med Genet 116B(1):41–44CrossRefPubMed
42.
43.
Kida H, Takano Y, Yamamoto K, Mori M, Yanaga K, Tanaka J, Kudo SE, Mimori K (2014) A single nucleotide polymorphism in fibronectin 1 determines tumor shape in colorectal cancer. Oncol Rep 32(2):548–552CrossRefPubMed
44.
Matalliotaki C, Matalliotakis M, Rahmioglu N, Mavromatidis G, Matalliotakis I, Koumantakis G, Zondervan K, Spandidos DA, Goulielmos GN, Zervou MI (2019) Role of FN1 and GREB1 gene polymorphisms in endometriosis. Mol Med Rep 20(1):111–116PubMedPubMedCentral
45.
Metadata
Title
Role of Fibronectin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants
Authors
Dawid Szpecht
Salwan R. Al-Saad
Lukasz M. Karbowski
Katarzyna Kosik
Grażyna Kurzawińska
Marta Szymankiewicz
Krzysztof Drews
Agnieszka Seremak-Mrozikiewicz
Publication date
01-08-2020
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 8/2020
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-020-04598-3

Other articles of this Issue 8/2020

Child's Nervous System 8/2020 Go to the issue

Case Report

Atlantoaxial instability treated with free-hand C1-C2 fusion in a child with Morquio syndrome

Cover Editorial

A skull in a skull: a child’s observation

Focus Session

Fetal therapy for congenital hydrocephalus—where we came from and where we are going

Focus Session

Not all ventriculomegaly is created equal: diagnostic overview of fetal, neonatal and pediatric ventriculomegaly

Invited Paper

Adamantinomatous craniopharyngioma in the molecular age and the potential of targeted therapies: a review

Case Report

Radiologically occult cervical intradural dermal sinus tract: a case report and review of literature