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Analysis of an Interleukin-6 Gene Promoter Polymorphism in Women With Endometriosis Polymorphism in Women With Endometriosis By Pyrosequencing

Gerhild Fabjani

Clemens Tempfer, MD

Christian Schneeberger, PhD

Michael Sator, MD

Johnnes Huber, MD

Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, and Division of Gynecology and Obstetrics, University of Vienna, Vienna, Austria

Rene Wenzl, MD

Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology & Reproductive Medicine, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria rene.wenzl{at}akh-wien.ac.at

Objective: Interleukin (IL)-6 has been implicated in the etiology of endometriosis. A single nucleotide polymorphism (SNP) at position -174 in the IL-6 gene promoter appears to influence IL-6 transcription rates in vitro and basal IL-6 levels in vivo. We determined the genotype and the allele frequencies of the -174 IL-6 promoter polymorphism and the corresponding IL-6 serum levels in women with endometriosis.

Methods: The pyrosequencing technique was used to assess the IL-6 genotypes in 94 women with histologically confirmed endometriosis (study gropu). A series of 70 healthy women without history of uterine disease served as clinical controls (control group).

Results: Allele frequencies for the G allele among women with and without endometriosis were 59.6% and 55.0% respectively (P = .430; odds ratio [OR] 0.83, 95% confidence interval [CI] 0.53, 1.29). Homozygotes for the protective allele C were present in 17.0% of women with endometriosis and in 18.6% of controls were homozygous for the protective allele C (P = .797; OR 0.90, 95% CI 0.40, 2.02). When patients with various disease manifestations wee compared, we found an association between the -174 G allele and chocolate cysts (P = .037). Serum levels of IL-6 were significantly higher in women with endometriosis than in controls (P < .001), with highest levels in women with chocolate cysts. There was no association between serum IL-6 levels and IL-6 genotype.

Conclusion: The IL-6 promoter polymorphism -174 G/C does not contribute significantly to ovoerall disease susceptibility but does predispose the carrier to distinct endometriosis with chololate cysts. A genetically determined high IL-6 response might play a pathogenic role in this disease condition.

Key Words: Endometriosis • polymorphism • interleukin-6 • pyrosequencing • chocolate cysts

Journal of the Society for Gynecologic Investigation, Vol. 10, No. 1, 32-36 (2003)
DOI: 10.1177/107155760301000107


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