Document Detail

Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth.
MedLine Citation:
PMID:  18951205     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To investigate the relation between 19 selected single nucleotide polymorphisms in three cytokine genes, tumor necrosis factor alpha (TNFA), interleukin 1-beta (IL1B) and interleukin 6 (IL6) and preterm birth (<37 weeks' gestation). DESIGN: Case-control association study. SAMPLE: A total of 117 singleton pregnant Danish Caucasian women, including 62 preterm birth cases and 55 controls (birth>or=37 weeks). METHODS: Genotyping was performed using TaqMan probes and traditional sequencing. Descriptive statistics were carried out with Fisher's exact test and Wilcoxon rank-sum test. All genetic data were tested for Hardy-Weinberg equilibrium and analyzed using logistic regression, 2x2 proportions or chi(2). Haplotypes were estimated for each gene and permutation used for association testing. RESULTS: Women carrying the TNFA -857 C>T rare allele (T) and those homozygous for the IL1B -31 T>C and IL1B -511 C>T rare alleles (C and T) have an increased risk of preterm birth with OR 3.1 (95% CI: 1.0-10.3) and OR 6.4 (95% CI: 1.3-60.5), respectively. Two estimated TNFA haplotypes were associated with preterm birth with OR 3.1 (p=0.037) and OR 2.7 (p=0.045). CONCLUSION: Polymorphisms in the cytokine genes TNFA and IL1B may increase the risk of preterm birth, possibly by a dysregulation of the immune system in pregnancy.
Mads Vilhelm Hollegaard; Jakob Grove; Poul Thorsen; Xiaobin Wang; Susanne Mandrup; Michael Christiansen; Bent Norgaard-Pedersen; Karen R Wojdemann; Ann Tabor; Jorn Attermann; David Michael Hougaard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta obstetricia et gynecologica Scandinavica     Volume:  87     ISSN:  1600-0412     ISO Abbreviation:  Acta Obstet Gynecol Scand     Publication Date:  2008  
Date Detail:
Created Date:  2008-12-09     Completed Date:  2009-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370343     Medline TA:  Acta Obstet Gynecol Scand     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  1285-90     Citation Subset:  IM    
Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
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MeSH Terms
Case-Control Studies
Interleukin-1beta / genetics*
Interleukin-6 / genetics
Logistic Models
Polymorphism, Single Nucleotide*
Premature Birth / genetics*
Promoter Regions, Genetic*
Transcription, Genetic
Tumor Necrosis Factor-alpha / genetics*
Reg. No./Substance:
0/Interleukin-1beta; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha

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