A Functional Promoter Polymorphism in NFKB1 Increases Susceptibility to Endometriosis

Abstract

Numerous proinflammatory cytokines, such as TNFα and IL-6, which are nuclear factor κB (NF-κB) target genes, have been shown to promote proliferation in endometriotic cells, and several other genes involved in promoting growth are also NF-κB target genes. The aim of this study was to investigate whether the functional insertion/deletion polymorphism (−94 insertion/deletion ATTG) in the promoter of nuclear factor κB gene (NFKB1) is associated with susceptibility to endometriosis. Polymerase chain reaction–polyacrylamide gel electrophoresis method was used to genotype the NFKB1 −94 insertion/deletion ATTG polymorphism in 206 women with endometriosis and 365 ethnicity-matched healthy control women. The genotyping method was confirmed by the DNA sequencing analysis. Genotype at the −94 insertion/deletion ATTG polymorphism in the NFKB1 promoter was in Hardy–Weinberg equilibrium in either case or control subjects. The frequency of the ATTG₂/ATTG₂ genotype and ATTG₂ allele in the endometriosis was significantly higher than that of control subjects (59.7% vs. 37%, odds ratio = 3.069, p < 0.001 for ATTG₂/ATTG₂ genotype; 75.2% vs. 59.7%, odds ratio = 2.049, p < 0.001 for ATTG₂ allele), indicating that the −94 insertion/deletion ATTG polymorphism in the NFKB1 promoter was associated with endometriosis. This study suggests that the functional −94 insertion/deletion ATTG polymorphism in the promoter of NFKB1 is associated with an increased risk for endometriosis.