title: Cytochrome P450 (CYP2D6) genotype is associated with elevated systolic blood pressure in preterm infants after discharge from the neonatal intensive care unit.
abstract: OBJECTIVE
  To determine genetic and clinical risk factors associated with elevated systolic blood pressure (ESBP) in preterm infants after discharge from the neonatal intensive care unit (NICU).
  
  
  METHODS
  A convenience cohort of infants born at <32 weeks gestational age was followed after NICU discharge. We retrospectively identified a subgroup of subjects with ESBP (systolic blood pressure [SBP] >90th percentile for term infants). Genetic testing identified alleles associated with ESBP. Multivariate logistic regression analysis was performed for the outcome ESBP, with clinical characteristics and genotype as independent variables.
  
  
  RESULTS
  Predictors of ESBP were cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) (rs28360521) CC genotype (OR, 2.92; 95% CI, 1.48-5.79), adjusted for outpatient oxygen therapy (OR, 4.53; 95% CI, 2.23-8.81) and history of urinary tract infection (OR, 4.68; 95% CI, 1.47-14.86). Maximum SBP was modeled by multivariate linear regression analysis: maximum SBP=84.8 mm Hg + 6.8 mm Hg if cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) CC genotype + 6.8 mm Hg if discharged on supplemental oxygen + 4.4 mm Hg if received inpatient glucocorticoids (P=.0002).
  
  
  CONCLUSIONS
  ESBP is common in preterm infants with residual lung disease after discharge from the NICU. This study defines clinical factors associated with ESBP, identifies a candidate gene for further testing, and supports the recommendation to monitor blood pressure before age 3 years, as is suggested for term infants.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA. john-dagle@uiowa.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Dagle
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Fisher
authors.forename: Susan E
authors.initials: SE
authors.lastname: Haynes
authors.forename: Susan K
authors.initials: SK
authors.lastname: Berends
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Brophy
authors.forename: Frank H
authors.initials: FH
authors.lastname: Morriss
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
mesh_terms: D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D008297:Male; D015999:Multivariate Analysis; D010102:Oxygen Inhalation Therapy; D010351:Patient Discharge; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013599:Systole; D014552:Urinary Tract Infections / Q000453:epidemiology
chemical_list: D005938:Glucocorticoids; D019389:Cytochrome P-450 CYP2D6