TY - JOUR
T1 - Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth
AU - Hollegaard, Mads Vilhelm
AU - Grove, Jakob
AU - Thorsen, Poul
AU - Wang, Xiaobin
AU - Mandrup, Susanne
AU - Christiansen, Michael
AU - Norgaard-Pedersen, Bent
AU - Wojdemann, Karen R
AU - Tabor, Ann
AU - Attermann, Jorn
AU - Hougaard, David Michael
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Adult
KW - Case-Control Studies
KW - Female
KW - Genotype
KW - Haplotypes
KW - Humans
KW - Interleukin-1beta
KW - Interleukin-6
KW - Logistic Models
KW - Polymorphism, Single Nucleotide
KW - Pregnancy
KW - Premature Birth
KW - Promoter Regions, Genetic
KW - Transcription, Genetic
KW - Tumor Necrosis Factor-alpha
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1080/00016340802468340
DO - 10.1080/00016340802468340
M3 - Journal article
C2 - 18951205
VL - 87
SP - 1285
EP - 1290
JO - Acta Obstetricia et Gynecologica Scandinavica
JF - Acta Obstetricia et Gynecologica Scandinavica
SN - 0001-6349
IS - 12
ER -