Relationship Between Tumor Necrosis Factor-Alpha Genotype and Success of Emergent Cerclage

ABSTRACT

The guanine to adenine substitution at the -308 position in the tumor necrosis factor-alpha (TNF-α) gene promoter region results in a 5-fold greater cytokine response to an inciting event. We investigated whether this polymorphism is associated with cervical incompetence and adverse pregnancy outcome after emergent cerclage. Women with a diagnosis of cervical incompetence requiring an emergent cerclage between 15 and 24 weeks were enrolled. Women without pregnancy complications were recruited as controls. DNA extraction from peripheral blood and polymerase chain reaction (PCR) amplification of a 144-base pair segment of the TNF-α gene were performed with subsequent sequencing. Twenty-three women underwent emergent cerclage and participated in the study, 13 (57%) of whom delivered after 28 weeks. Twenty-three women served as controls. There were no differences in the TNF-α polymorphism between women with cervical incompetence and controls or between women with cervical incompetence who delivered before versus after 28 weeks. The TNF-α polymorphism was not associated with cervical incompetence or with delivery prior to 28 weeks in women who received an emergent cerclage.

KEYWORDS

Cervical incompetence - emergent cerclage - tumor necrosis factor-alpha genotype

REFERENCES

• 1 Iams J. Cervical incompetence. In: Creasy R, Resnik R, eds. Maternal-Fetal Medicine Philadelphia: WB Saunders 1999: 445-464
• 2 Ansari A H, Reynolds R A. Cervical incompetence: a review.  J Reprod Med . 1987;  32 161-171
• 3 Golan A, Barnan R, Wexler S, Langer R, Bukovsky I, David M P. Incompetence of the uterine cervix.  Obstet Gynecol Surv . 1989;  44 96-107
• 4 Romero R, Gonzalez R, Sepulveda W. et al . Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance.  Am J Obstet Gynecol . 1992;  167 1086-1091
• 5 Oberholzer A, Oberholzer C, Moldawer L. Cytokine signaling-regulation of the immune response in normal and critically ill states.  Crit Care Med . 2000;  28 N3-N12
• 6 Romero R, Mazor M, Sepulveda W, Copeland D, Williams J. Tumor necrosis factor in preterm and term labor.  Am J Obstet Gynecol . 1992;  166 1576-1587
• 7 Hillier S L, Witkin S S, Krohn M A, Watts D N, Kiviat N B, Eschenbach D A. The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histiologic chorioamnionitis, and chorioamnion infection.  Obstet Gynecol . 1993;  81 941-948
• 8 Goldenberg R, Hauth J, Andrews W. Mechanisms of disease: intrauterine infection and preterm delivery.  N Engl J Med . 2000;  342 1500-1507
• 9 Wilson A G, di Giovine S F, Blakemore A I, Duff G W. Single base polymorphism in the human tumor necrosis factor alpha (TNF-α) gene detectable by NcoI restriction of PCR product.  Hum Mol Genet . 1992;  1 353
• 10 Wilson A G, Symons J A, McDowell T L, McDevitt H O, Duff G W. Effects of a polymorphism in the tumor necrosis factor α promoter on transcriptional activation.  Proc Natl Acad Sci U S A . 1997;  94 3195-3199
• 11 McGuire W, Hill A VS, Allsopp C EM, Greenwood B M, Kwiatkowski D. Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria.  Nature . 1994;  371 508-511
• 12 Mira J, Cariou A, Grall F. et al . Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study.  JAMA . 1999;  282 561-568
• 13 Dizon-Townson D, Major H, Varner M, Ward K. A promoter mutation that increases transcription of the tumor necrosis factor-α gene is not associated with preterm delivery.  Am J Obstet Gynecol . 1997;  177 810-813
• 14 Roberts A, Monzon-Bordonaba F, Van Deerlin P. et al . Association of polymorphism within the promoter of the tumor necrosis factor α gene with increased risk of preterm premature rupture of the fetal membranes.  Am J Obstet Gynecol . 1999;  180 1297-1302
• 15 Macones G, Parry S, Marder S. et al . Evidence of a gene-environment interaction in the etiology of spontaneous preterm birth.  Am J Obstet Gynecol . 2001;  184 S3
• 16 Novy M, Gupta A, Wothe D, Gupta S, Kennedy K, Gravett M. Cervical cerclage in the second trimester of pregnancy: a historical cohort study.  Am J Obstet Gynecol . 2001;  184 1447-1456
• 17 Olatunbosum O A, al-Nuaim L, Turnell R W. Emergency cerclage compared with bedrest for advanced cervical dilation in pregnancy.  Int Surg . 1995;  80 170-174
• 18 Schorr S, Morales W. Obstetric management of incompetent cervix and bulging fetal membranes.  J Reprod Med . 1996;  41 235-238
• 19 MacDougall J, Siddle N. Emergency cervical cerclage.  Br J Obstet Gynaecol . 1991;  98 1234-1238
• 20 Chasen S, Siverman N. Mid-trimester emergent cerclage: a ten year single institution review.  J Perinatol . 1998;  18 338-342
• 21 Aarts J, Brons J, Bruinse H. Emergency cerclage: a review.  Obstet Gynecol Surv . 1995;  50 459-469
• 22 Kurup M, Goldkrand J. Cervical incompetence: elective, emergent, or urgent cerclage.  Am J Obstet Gynecol . 1999;  181 240-246