Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth

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

    30 Citationer (Scopus)

    Abstract

    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.

    OriginalsprogEngelsk
    TidsskriftActa Obstetricia et Gynecologica Scandinavica
    Vol/bind87
    Udgave nummer12
    Sider (fra-til)1285-90
    Antal sider6
    ISSN0001-6349
    DOI
    StatusUdgivet - 2008

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