Analysis of an interleukin-6 gene promoter polymorphism in women with endometriosis by pyrosequencing

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 group). A series of 70 healthy women without history of uterine disease served as clinical controls (control groups). 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 were 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 overall disease susceptability but does predispose the carrier to distinct endometriosis with chocolate cysts. A genetically determined high IL-6 response might play a pathogenic role in this disease condition.