Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

Pankaj Prasun; Raghav Madan; Subhash Puthuraya; Divya Subramanian; Ishita Datta; Vaneet Kalra; Ronald Thomas; David W Stockton; Senthil Sundaram; Joseph Callaghan; Michael Callaghan; Nitin Chouthai

doi:10.1159/000493788

Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

Dev Neurosci. 2018;40(4):337-343. doi: 10.1159/000493788. Epub 2018 Nov 2.

Authors

Affiliations

¹ Department of Genetics and Genomic Sciences, Icahn School of Medicine, New York, New York, USA.
² School of Medicine, Wayne State University, Detroit, Michigan, USA.
³ Division of Neonatology, Cleveland Clinic Children's Hospital, Cleveland, Ohio, USA.
⁴ College of Medicine, Ohio State University, Columbus, Ohio, USA.
⁵ Division of Pediatric Hematology/Oncology, Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan, USA.
⁶ Division of Neonatology, UCSF Benioff Children's Hospital, Oakland, California, USA.
⁷ Division of Genetic, Genomic, and Metabolic Disorders, Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan, USA.
⁸ Division of Accounting, Oakland University, Rochester, Michigan, USA.
⁹ Division of Pediatric Hematology/Oncology, Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan, USA, nchoutha@med.wayne.edu.

PMID: 30391947
DOI: 10.1159/000493788

Abstract

Background: The pathophysiology of intraventricular hemorrhage (IVH) is multifactorial. This study attempts to identify genetic and clinical factors contributing to IVH in newborns with a focus on those born ≤28 weeks of gestation.

Methods: This was a prospective study of 382 consecutive newborns admitted to the neonatal intensive care unit. DNA purification was conducted using standard methods. TaqMan SNP assays were conducted for functional polymorphisms in VEGF (RS699947, RS2010963, RS3025039, and RS1570360) and MMP2 (RS243685 and RS2285053) genes. An RFLP assay was done for a polymorphism in MMP9 (RS3918242).

Results: The GG genotype in VEGF RS1570360 (p = 0.013) and the CC genotype in VEGF RS699947 (p = 0.036) were associated with a lower incidence of IVH amongst newborns ≤28 weeks of gestation. Chorioamnionitis, Caucasian race, and patent ductus arteriosus were associated with a higher incidence of IVH. A binary logistic regression analysis of clinical and SNP data that was significant from bivariate analysis demonstrated that VEGF RS1570360 was significantly associated with IVH (p = 0.017).

Conclusion: This study demonstrated that the GA/AA genotype in VEGF RS1570360 and the AA/AC genotype in VEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examine VEGF polymorphisms in association with IVH.

Keywords: Growth factors; Intraventricular hemorrhage; MMP; Pathogenesis; VEGF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cerebral Hemorrhage / genetics*
Female
Genetic Predisposition to Disease / genetics*
Genotype
Humans
Infant, Extremely Premature / growth & development
Infant, Newborn
Male
Matrix Metalloproteinases / genetics*
Polymorphism, Single Nucleotide / genetics
Pregnancy
Prospective Studies
Vascular Endothelial Growth Factor A / genetics*

Substances

Vascular Endothelial Growth Factor A
Matrix Metalloproteinases