Haplotype analysis of the matrix metalloproteinase-9 gene associated with advanced-stage endometriosis

Objective: To investigate whether the -1562C>T, R279Q, P574R, and R668Q polymorphisms of the matrix metalloproteinase-9 (MMP-9) gene are related to endometriosis. Design: Case-control study. Setting: University-based hospital in Korea. Patient(s): Patients with endometriosis stage III/IV (n = 225) who underwent pelvic surgery and controls (n = 198) with no endometriosis in a Korean population. Intervention(s): Peripheral blood samples were collected by venipuncture. Main Outcome Measure(s): Frequencies of genotypes and haplotypes were compared with the risk of endometriosis including -1562C>T, R279Q, P574R, and R668Q polymorphisms of MMP-9. Result(s): In the two-locus haplotype analyses using the four single nucleotide polymorphisms (SNPs), an increase in the distribution of the R279Q/P574R (2678G>A/4859C>G) (AC haplotype: odds ratio [OR] = 3.180, 95% confidence interval [CI] = 1.956-5.170; GG haplotype: OR = 4.374, 95% CI = 2.376-8.053) and -1562C>T/R668Q (-1562C>T/5546G>A) (CA haplotype: OR = 3.280, 95% CI = 1.406-7.653) haplotypes was significantly associated with endometriosis. By contrast, the risk of endometriosis was not associated with the individual SNPs studied. Conclusion(s): These findings suggest that haplotype analysis was more informative than SNP analysis. The haplotypes in the MMP-9 gene may correlate with the progression of endometriosis, and further study of these variations might improve our understanding of the pathogenesis of endometriosis.