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Background: We have recently identified a homozygous nucleotide substitution in exon 30 of type III collagen (COL3A1 2209G>A, rs1800255) as a risk factor for the development of pelvic organ prolapse. This polymorphism is also associated with mitral valve prolapse. Patients could benefit from preventive actions when identified prior to clinical evidence of the disease. High resolution melting (HRM) analysis is a low-cost, high-throughput technique to identify DNA polymorphisms. The purpose of this study was to investigate whether HRM is an accurate method to detect the above mentioned polymorphism in DNA from blood samples Methods: A total of 36 randomly selected DNA samples from pelvic organ prolapse patients were analyzed in duplicate using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (PCR-RFLP) and sequence analysis. Using the latter as the gold standard, all samples were subjected to HRM analysis with the use of specific primers and an unlabelled probe. Results: Compared to sequence analysis, PCR-RFLP resulted in 2 incorrect diagnoses. High resolution melting analysis demonstrated unique melting profiles for wild-type, as well as heterozygous and homozygous polymorphisms, with 100% accuracy. Conclusion: High resolution melting is a fast, cost-effective, and sensitive screening method to detect the rs1800255 polymorphism. [ABSTRACT FROM AUTHOR]

Objective: There is evidence that both environmental and genetic factors contribute to pelvic organ prolapse. We conducted a genome-wide association study to investigate whether common genetic variants modify the risk of pelvic organ prolapse., Methods: We recruited women who had been evaluated and treated for pelvic organ prolapse at the University of Utah from 1996 to 2008 and their affected female relatives. Those in the case group were genotyped on the Illumina 550K platform. We genetically matched 2,976 white control participants available from Illumina as the control group. Association tests were adjusted for related participants using two different software programs: EMMAX and Genie. Confirmation of findings was performed in a cohort of Dutch women (n=76) with recurrent pelvic organ prolapse and family history of pelvic organ prolapse., Results: The Utah study sample included 115 case group participants treated for pelvic organ prolapse, in most case group participants with surgery (n=78) or repeat surgery (n=35). Results from association analyses using EMMAX software identified five single-nucleotide polymorphisms (SNPs) significantly associated with pelvic organ prolapse (P<1×10). Independent association analysis with Genie software identified three of the same SNPs and one additional SNP. The six SNPs were located at 4q21 (rs1455311), 8q24 (rs1036819), 9q22 (rs430794), 15q11 (rs8027714), 20p13 (rs1810636), and 21q22 (rs2236479). Nominally significant findings (P<.05) or findings trending toward significance (P<.1) were observed for five of the six SNPs in the Dutch cohort., Conclusion: Six SNPs have been identified that are significantly associated with pelvic organ prolapse in high-risk familial case group participants and that provide evidence for a genetic contribution to pelvic organ prolapse., Level of Evidence: II.