O-28: Endometriosis Is Influenced by The Promoter Haplotype-Based Expression of Macrophage Migration Inhibitory Factor (MIF)

Background: Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine that is secreted by accumulated active macrophages in ectopic tissue of endometriosis. MIF is involved in pathophysiological events of endometriosis, such as angiogenesis and cell proliferation. MIF that stimulates the synthesis of PGE2, leads to over-expression of local estradiol synthesis in endometriosis. Materials and Methods: Genomic DNA of 70 patients with endometriosis, who had undergone laparoscopy during 2012- 13, and 70 fertile women were amplified via PCR. Restriction fragment length polymorphism which was applied to determine -173G/C polymorphism. ORF polymorphisms and -794(CATT)5-8 were detected by sequencing. Q- PCR was performed for mRNA expression level of MIF in 14 ectopic tissues. Statistical analysis was done by Chi-square test and one way ANOVA. Results: The genotype analysis of ORF polymorphisms revealed three SNPs: +254, rs2096525 (p=0.84), +656, rs2070766 (p=0.88),+626, rs33958703 (p=0.04). Homozygocity of -794(CATT)5, as normal type, was only observed in control group. Promoter haplotype (-173G/C and -794(CATT)5-8) was different in control and patient groups. Expression level of MIF in ectopic tissues with -794(CATT)6,7/- 173GC was significantly more than the other haplotypes (p=0.00) and in -794(CATT)6,6/-173GC group was significantly higher than -794(CATT)5,5/-173G (p=0.02). We found maximum prevalence of endometriosis at those being 26-30 years. Obese women with BMI≥30 have shown lower risk of endometriosis (p=0.00). Conclusion: We report for the first time, both increased number of CATT repeat in -794 and presence of -173 C in ectopic tissue of endometriosis stimulated MIF promoter activity. It seems haplotype of -794(CATT)5-8/-173G/C and +626 rs33958703 SNP were significantly correlated with susceptibility of endometriosis that might play an important role in pathophysiology of endometriosis.