OBJECTIVE: Evaluate possible association of genetic variability detected via single nucleotide polymorphisms (SNPs) and pelvic organ prolapse (POP). METHODS: Thirty six women with stage III-IV POP and 36 controls matched for race, age, parity, and body mass index were recruited. Blood DNA was genotyped for 9 SNPs (matrix metalloproteinases, MMP1, 2, 3, 8, 9, 10, 11, and TIMP1 and 2). Association of each SNP and gene frequencies by group were computed, and haplotype frequencies were estimated. RESULTS: All subjects were white with comparable age, parity, and weight. Sixty-two percent of cases and 38% of controls had previous hysterectomy (P < 0.00). Genotypic frequencies differed between groups for MMP10 (P = 0.01). The C allele for MMP10 was present in 19.4% of controls and absent in cases. Haplotyping indicated significant linkage between MMP10 and all others except MMP2. CONCLUSIONS: The C allele for MMP10 may provide some protection against prolapse. MMP10 demonstrates significant linkage with multiple metalloproteinases tested in this study: MMP1, MMP3, MMP8, MMP9, TIMP1, and TIMP3. Further studies will be necessary to test the clinical significance of this observation. © 2008 Lippincott Williams & Wilkins, Inc.