The novel gene-wide haplotype at the macrophage migration inhibitory factor (MIF) locus is associated with endometrioma

Abstract Objective Endometriosis is a common complex gynecological disorder that may result in infertility. Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine that is overexpressed in endometriosis tissues. However, hitherto, no study tested the possible relevancy at genetic level. The aim of this study was to evaluate MIF polymorphisms and possible associations between haplotype of the gene and endometrioma. Study Design In this experiment, 115 patients with confirmed endometrioma and 120 of women who were not diagnosed with endometrioma were recruited for this case-control genetic association study. The coding region of MIF was resequenced to detect variations of potential significance. Restriction fragment length polymorphism was used to type the −173 G/C (rs755622) promoter Single nucleotide polymorphism (SNP). Haplotype analyses were then undertaken to assess the effect of genetic variations. Results We detected one functional SNP in promoter (rs755622) and non-functional mutations across the gene including (rs2096525, rs182012324, rs33958703 and rs2070766) in our samples. However, haplotype analysis showed a significant association between MIF and endometrioma where a single haplotype CC carrying only the minor allele at −173 G/C was significantly over-represented in the patients group (P = 0.007) and remained significant even after correction for multiple testing (R: adjusted P = 0.0299). Conclusion We report a strong linkage between a novel MIF haplotype and endometrioma. This association is consistent with expression data at both transcript and protein levels suggesting the -173C/G promoter as a critical factor.