The genetic susceptibility to retinopathy of prematurity. M. Bizzarro1, N. Hussain2, B. Jonsson3, R. Feng4, L. Ment1, J. Gruen1,5, H. Zhang4, V. Bhandari1. 1) Dept Pediatrics, Yale Univ Sch Medicine, New Haven, CT; 2) Division of Neonatology, University of Connecticut Health Center, Farmington, CT; 3) Department of Neonatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; 4) Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT; 5) Department of Genetics and the Yale Child Health Research Center, New Haven, CT.
Background: Retinopathy of prematurity (ROP) accounts for significant morbidity in preterm neonates. In addition to prematurity and environmental factors, we hypothesized that genetic factors play a significant role in this disease process.
Objective:To isolate and estimate the genetic susceptibility to ROP
Patients and Methods: A retrospective study (1994-2004) from 3 centers was performed using zygosity data from premature twins born at 32 weeks gestational age (GA) and surviving beyond 36 weeks postmenstrual age. ROP was diagnosed and staged by pediatric ophthalmologists at each center. Data analyses were performed using mixed effect logistic regression (MELR) analysis and latent variable probit modeling.
Results: 63 monozygotic (MZ) and 137 dizygotic (DZ) twin pairs were identified and analyzed. Demographic data for GA, birth weight, gender, respiratory distress syndrome, ROP, bronchopulmonary dysplasia, duration of ventilation and supplemental oxygen use, and length of stay were comparable between MZ and DZ twins. In the MELR for ROP, GA (p=0.024, OR 0.65; 95% CI=0.45-0.94) and duration of supplemental oxygen (p=0.003, OR=1.03; 95%CI=1.01-1.05) were significant covariates. After controlling for known and unknown non-genetic factors, genetic factors accounted for 70.1% (95%CI=0.09-1.00; p=0.026) of the variance in liability for ROP.
Conclusion: Besides environmental factors, there is a strong genetic predisposition to ROP.