Cytokine Gene Polymorphisms and Length of Gestation

OBJECTIVE: To estimate whether there is an association between length of gestation and gene polymorphisms that effect transcription of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), or interleukin-1 beta (IL-1 beta). 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-alpha -308, IL-6 -174, and IL-1 beta +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-alpha 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-1 beta +3954 SNP. CONCLUSION: Polymorphism at the -308 position in the TNF-alpha promoter region is associated with shorter gestation and an increased risk of spontaneous extreme preterm delivery.