title: IL-18R1 and IL-18RAP SNPs may be associated with bronchopulmonary dysplasia in African-American infants.
abstract: BACKGROUND
  The genetic contribution to the development of bronchopulmonary dysplasia (BPD) in prematurely born infants is substantial, but information related to the specific genes involved is lacking.
  
  
  RESULTS
  Genotype analysis revealed, after multiple comparisons correction, two significant single-nucleotide polymorphism (SNPs), rs3771150 (IL-18RAP) and rs3771171 (IL-18R1), in African Americans (AAs) with BPD (vs. AAs without BPD; q < 0.05). No associations with Caucasian (CA) BPD, AA or CA respiratory distress syndrome (RDS), or prematurity in either AAs or CAs were identified with these SNPs. Respective frequencies were 0.098 and 0.093 in infants without BPD and 0.38 for each SNP in infants with BPD. In the replication set (82 cases; 102 controls), the P values were 0.012 for rs3771150 and 0.07 for rs3771171. Combining P values using Fisher's method, overall P values were 8.31 × 10(-7) for rs3771150 and 6.33 × 10(-6) for rs3771171.
  
  
  CONCLUSIONS
  We conclude that IL-18RAP and IL-18R1 SNPs identify AA infants at risk for BPD. These genes may contribute to AA BPD pathogenesis via inflammatory-mediated processes and require further study.
  
  
  METHODS
  We conducted a case-control SNP association study of candidate genes (n = 601) or 6,324 SNPs in 1,091 prematurely born infants with gestational age <35 weeks, with or without neonatal lung disease including BPD. BPD was defined as a need for oxygen at 28 days.
authors.affiliation: Department of Pediatrics and CHILD Research, Penn State College of Medicine, Hershey, Pennsylvania, USA. jfloros@psu.edu
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
authors.forename: Douglas
authors.initials: D
authors.lastname: Londono
authors.forename: Derek
authors.initials: D
authors.lastname: Gordon
authors.forename: Patricia
authors.initials: P
authors.lastname: Silveyra
authors.forename: Susan L
authors.initials: SL
authors.lastname: Diangelo
authors.forename: Rose M
authors.initials: RM
authors.lastname: Viscardi
authors.forename: George S
authors.initials: GS
authors.lastname: Worthen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shenberger
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Lin
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001997:Bronchopulmonary Dysplasia / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005865:Gestational Age; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D053727:Interleukin-18 Receptor alpha Subunit / Q000235:genetics*; D053728:Interleukin-18 Receptor beta Subunit / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics*
chemical_list: C508572:IL18R1 protein, human; C115629:IL18RAP protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D053728:Interleukin-18 Receptor beta Subunit