title: Candidate gene linkage approach to identify DNA variants that predispose to preterm birth.
abstract: BACKGROUND
  The aim of this study was to identify genetic variants contributing to preterm birth (PTB) using a linkage candidate gene approach.
  
  
  METHODS
  We studied 99 single-nucleotide polymorphisms (SNPs) for 33 genes in 257 families with PTBs segregating. Nonparametric and parametric analyses were used. Premature infants and mothers of premature infants were defined as affected cases in independent analyses.
  
  
  RESULTS
  Analyses with the infant as the case identified two genes with evidence of linkage: CRHR1 (P = 0.0012) and CYP2E1 (P = 0.0011). Analyses with the mother as the case identified four genes with evidence of linkage: ENPP1 (P = 0.003), IGFBP3 (P = 0.006), DHCR7 (P = 0.009), and TRAF2 (P = 0.01). DNA sequence analysis of the coding exons and splice sites for CRHR1 and TRAF2 identified no new likely etiologic variants.
  
  
  CONCLUSIONS
  These findings suggest the involvement of six genes acting through the infant and/or the mother in the etiology of PTB.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Elise N A
authors.initials: EN
authors.lastname: Bream
authors.forename: Cara R
authors.initials: CR
authors.lastname: Leppellere
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.forename: John M
authors.initials: JM
authors.lastname: Dagle
authors.forename: David C
authors.initials: DC
authors.lastname: Merrill
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Hyagriv N
authors.initials: HN
authors.lastname: Simhan
authors.forename: Chin-To
authors.initials: CT
authors.lastname: Fong
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Muglia
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
mesh_terms: D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D003718:Denmark; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D047928:Premature Birth / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics; D014481:United States; D000099052:CRF Receptor, Type 1
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018019:Receptors, Corticotropin-Releasing Hormone; D047992:TNF Receptor-Associated Factor 2; D000099052:CRF Receptor, Type 1; D019392:Cytochrome P-450 CYP2E1; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases