Skeletal muscle heavy-chain polypeptide 3 and myosin binding protein H in the pubococcygeus muscle in patients with and without pelvic organ prolapse

Abstract

The purpose of this study was to compare gene expression of skeletal muscle heavy-chain polypeptide 3 (MYH3) and myosin binding protein H (MyBP-H) in the pubococcygeus muscle of patients with pelvic organ prolapse and controls. Genes previously identified by microarray genechip analysis of pubococcygeus muscle biopsies were examined using real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Specimens were obtained from 17 patients with stage III or IV pelvic organ prolapse and 23 controls with minimal to no prolapse. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as the housekeeping gene. Samples and controls were run in triplicate in separate wells, and the levels of gene expression were analyzed quantitatively using the comparative critical threshold (Ct) method. Differences in gene expression were analyzed using Wilcoxon rank-sum testing. Significant differences in gene expression were observed between patients with prolapse and controls for both genes. Skeletal muscle myosin heavy-chain polypeptide 3 was 6.5 times underexpressed in patients with pelvic organ prolapse compared to controls (P = .028). Similarly, myosin binding protein H was 3.2 times underexpressed in patients with prolapse (P = .042). Overall, patients had a mean age of 62.4 +/- 6.5 years compared with controls with a mean age of 45.3 +/- 7.4 years (P < .001), so analysis was also performed on an age-matched subset of 8 patients and controls (mean ages of 58.1 +/- 5.4 years and 53.3 +/- 5.0 years, respectively, P = .02) with similar results. Prolapse patients in this subset were similar in parity and race to controls but had lower body mass index (23.2 vs 29.9, P = .04). MYH3 was 10.9 times underexpressed in patients with pelvic organ prolapse compared to controls (P = .027). MyBP-H was 10.4 times underexpressed in patients with prolapse (P = .036). These findings suggest that the differences between patients with advanced pelvic organ prolapse and controls may be related to differential gene expression of structural proteins related to myosin. Specifically, advanced pelvic organ prolapse may be related to down-regulation of skeletal muscle heavy-chain polypeptide 3 and myosin binding protein H.