Tumor necrosis factor-alpha promoter gene polymorphism -308 and chorioamnionitis.
OBJECTIVE
A single-base polymorphism within the promoter of the gene for tumor necrosis factor alpha at position -308 relative to the transcriptional start site of the gene is correlated with differences in production of tumor necrosis factor alpha. There are two allelic forms: TNFA1 and TNFA2. The TNFA2 allele is associated with increased production of tumor necrosis factor alpha. The purpose of this study is to assess the relationship between carriage of the TNFA2 allele and clinical chorioamnionitis.


METHODS
In this retrospective cohort study, previously banked deoxyribonucleic acid from 149 women who had spontaneous labor from 37 to 42 weeks' gestation was used. Polymerase chain reaction was used for polymorphism assay. Demographic and clinical information was obtained from the medical record. Clinical chorioamnionitis was defined as at least one temperature elevation above 38C combined with at least two of the following signs: maternal or fetal tachycardia, uterine tenderness greater than expected, foul-smelling vaginal discharge, and white blood cell count more than 18,000.


RESULTS
Chorioamnionitis was present in 18 women (12.1%). Among women who did not carry TNFA2, the chorioamnionitis rate was 7.4%. Among women who carried TNFA2, the chorioamnionitis rate was 24.4%. The relative risk for chorioamnionitis with carriage of TNFA2 was 3.3 (95% confidence interval 1.3, 7.1). This increased risk was not altered after adjustment for race, type of rupture of membranes, intrauterine pressure catheter use, smoking, and prolonged rupture of membranes.


CONCLUSIONS
Carriage of the TNFA2 allele is associated with a more than three-fold increased risk of clinical chorioamnionitis, even when accounting for important clinical and microbiologic risk factors.
Simhan
Hyagriv N
HN
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. hsimhan@mail.magee.edu
Krohn
Marijane A
MA
Zeevi
Adriana
A
Daftary
Ashi
A
Harger
Gail
G
Caritis
Steve N
SN
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002821:Chorioamnionitis / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D016015:Logistic Models; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis*; D011256:Pregnancy Outcome; D011336:Probability; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha