WIP 01 - Are Genetic Variants from the Asthma Gene ORMDL3 Associated with the Development of Bronchopulmonary Dysplasia in ELBW Infants?: A Pilot Study

Publication Number: WIP 01.7600

Gayathri Sreenivasan, Maria Fareri Children's Hospital at Westchester Medical Center, Astoria, NY, United States; Sarah Ampalloor, New York Medical College, New York, NY, United States; Shreya Bhandari, Maria Fareri Children's Hospital at Westchester Medical Center, Lansdale, PA, United States; Haedyn Christie, Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, NY, United States; Lance Parton, MFCH at WMC, Valhalla, NY, United States

Background: The gene ORMDL3 has been shown to be associated with early-onset asthma susceptibility in multiple independent genome-wide and candidate-gene association studies. Bronchopulmonary dysplasia (BPD) has a strong genetic component, is linked with prematurity, and is often associated with a family history of asthma, as well as an increased susceptibility to reactive airway disease. The orosomucoid-like protein 3 (ORMDL3) gene regulates the activity of serine palmitoyl transferase (SPT), the first and rate-limiting enzyme for sphingolipid biosynthesis in cells. Altered ORMDL3 expression has a pathogenic role in asthma, and candidate gene variants of ORMDL3 have been associated with alterations of expression as well as susceptibility to asthma.

Objective: To examine the association of variants of the ORMDL3 with BPD in extremely low birth weight (ELBW) infants.

Design/Methods: This is a prospective observational, cohort study including ELBW infants, defined as birth weight less than 1000g, with or without BPD, defined as oxygen-dependence at 36 weeks PMA. Written parental consent was obtained following approval by the IRBs at NYMC and WMC (#8859). DNA was isolated from buccal swabs and subjected to RT-PCR with specific TaqMan probes for ORMDL3 gene variants. We tested variants rs4065275, rs12603332 and rs8076131. Chi-square, Fisher’s exact, and z-tests were used for categorical variables; Mann-Whitney U-test and t-test were used for continuous variables; with p< 0.05 statistically significant. The sample population was analyzed and were similar with no statistical difference between the BPD and noBPD groups. Preliminary genetic analyses were done. While we did not find associations with these candidate gene variants of ORMDL3 so far, this is a pilot study with initial limited sample size, and further infants are in the process of being analyzed. We speculate that ORMDL3 variants may result in an increased susceptibility to BPD and reactive airway disease by altering sphingolipid biosynthesis.