title: Cytokine gene polymorphisms and length of gestation.
abstract: OBJECTIVE
  To estimate whether there is an association between length of gestation and gene polymorphisms that effect transcription of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or interleukin-1β (IL-1β).
  
  
  METHODS
  Blood for DNA analysis was collected from 834 women at high risk enrolled in a randomized, clinical trial of omega-3 fatty acid supplementation for the prevention of recurrent preterm birth. Genotyping was performed for three single nucleotide polymorphisms (SNPs), TNF-α -308, IL-6 -174, and IL-1β +3954. Women with the homozygous minor genotype were compared with women with either the heterozygous or the homozygous major genotype. Kaplan-Meier curves of gestational age at delivery and odds ratios for extreme preterm delivery were adjusted for African-American race and treatment group.
  
  
  RESULTS
  Women who were homozygous for the minor allele at the -308 position in the promoter region of the TNF-α gene had significantly shorter length of gestation than women who were either heterozygous or homozygous for the major allele (adjusted hazard ratio 1.74, 95% confidence interval [CI] 1.04-2.90, P=.03). Among women with this genotype, 20% (3/15) experienced extreme spontaneous preterm delivery (less than 28 weeks of gestation; adjusted odds ratio 7.51, 95% CI 1.84-30.72, P=.005). There was no difference in length of gestation or risk of extreme spontaneous preterm delivery by genotype for the IL-6 -174 or the IL-1β +3954 SNP.
  
  
  CONCLUSIONS
  Polymorphism at the -308 position in the TNF-α promoter region is associated with shorter gestation and an increased risk of spontaneous extreme preterm delivery.
  
  
  BACKGROUND
  ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902.
  
  
  METHODS
  II.
authors.affiliation: From the Department of Obstetrics and Gynecology and the Center for Human Genomics at Wake Forest University Health Sciences, Winston-Salem, North Carolina; the Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Wayne State University, Detroit, Michigan; the University of Utah Health Sciences Center, Salt Lake City, Utah; The Ohio State University, Columbus, Ohio; Northwestern University, Chicago, Illinois; Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio; the University of Alabama at Birmingham, Birmingham, Alabama; the University of Texas Health Science Center at Houston, Houston, Texas; the University of Texas Medical Branch, Galveston, Texas; The George Washington University Biostatistics Center, Washington DC; the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: Margaret
authors.initials: M
authors.lastname: Harper
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thom
authors.forename: Mark A
authors.initials: MA
authors.lastname: Klebanoff
authors.forename: John
authors.initials: J
authors.lastname: Thorp
authors.forename: Yoram
authors.initials: Y
authors.lastname: Sorokin
authors.forename: Michael W
authors.initials: MW
authors.lastname: Varner
authors.forename: Jay D
authors.initials: JD
authors.lastname: Iams
authors.forename: Mara
authors.initials: M
authors.lastname: Dinsmoor
authors.forename: Brian M
authors.initials: BM
authors.lastname: Mercer
authors.forename: Dwight J
authors.initials: DJ
authors.lastname: Rouse
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ramin
authors.forename: Garland D
authors.initials: GD
authors.lastname: Anderson
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha