The candidate's long-term career goal is to become an independent researcher who will integrate methods in genetic epidemiology with those used in health services and clinical epidemiology to improve the care of neonates.Respiratory Distress Syndrome (RDS) is the major cause of morbidity and mortality in premature infants.The primary etiology of the RDS is developmental immaturity of surfactant production. However, there issignificant heterogeneity in pulmonary outcomes among infants of the same gestational age who havesimilar clinical risk factors. Studies suggest a significant genetic contribution to the risk of RDS. Geneticvariations that are clinically insignificant among term infants may contribute to preterm infants'susceptibility to RDS.
The specific aims of the proposal are 1) to examine if common genetic variations(single nucleotide polymorphisms) in the genes that code for Surfactant Proteins A, B, and C and ATPbinding cassette transporter 3 are associated with RDS, and 2) to evaluate if severity of RDS isassociated with these genetic variations. To accomplish these aims, we will employ a unique setting, theNorthern California Kaiser Permanente Medical Care Program, which has a large defined population(>35,000 births/year), integrated information systems, and readily available critical information includingan electronic medical record, radiology results, and laboratory test results. Using a nested case controldesign, we will obtain DMAsamples from infants with RDS (n~160) and controls matched by gestationalage, gender, and ethnicity. Conditional multivariate logistic regression techniques will be used toevaluate for associations between these genetic variants and RDS. In the infants with RDS, we will usemultivariate linear regression techniques to compare measures of RDS severity (duration ofsupplemental oxygen use and duration of assisted ventilation) between infants who have genetic variantsand those who do not, controlling for confounders such as gestational age.Common variations in an infant's genetic code may explain why some infants develop RDS or have moresevere disease. This variation may not be important unless the infant is born prematurely or has otherrisk factors. Knowing if an infant has any of these common variations may allow physicians to customizeprevention and treatment strategies, based upon this genetic information.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
7K23HD055963-03
Application #
8192179
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Raju, Tonse N
Project Start
2009-09-30
Project End
2014-08-31
Budget Start
2010-09-03
Budget End
2011-08-31
Support Year
3
Fiscal Year
2010
Total Cost
$125,335
Indirect Cost
Name
Kaiser Foundation Research Institute
Department
Type
DUNS #
150829349
City
Oakland
State
CA
Country
United States
Zip Code
94612
Anadkat, J S; Kuzniewicz, M W; Chaudhari, B P et al. (2012) Increased risk for respiratory distress among white, male, late preterm and term infants. J Perinatol 32:780-5