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Background: Black women are at an increased risk of developing uterine leiomyomas and experiencing worse disease prognosis than White women. Epidemiologic and molecular factors have been identified as underlying these disparities, but there remains a paucity of deep, multiomic analysis investigating molecular differences in uterine leiomyomas from Black and White patients., Objective: To identify molecular alterations within uterine leiomyoma tissues correlating with patient race by multiomic analyses of uterine leiomyomas collected from cohorts of Black and White women., Study Design: We performed multiomic analysis of uterine leiomyomas from Black (42) and White (47) women undergoing hysterectomy for symptomatic uterine leiomyomata. In addition, our analysis included the application of orthogonal methods to evaluate fibroid biomechanical properties, such as second harmonic generation microscopy, uniaxial compression testing, and shear-wave ultrasonography analyses., Results: We found a greater proportion of MED12 mutant uterine leiomyomas from Black women (>35% increase; Mann-Whitney U, P<.001). MED12 mutant tumors exhibited an elevated abundance of extracellular matrix proteins, including several collagen isoforms, involved in the regulation of the core matrisome. Histologic analysis of tissue fibrosis using trichrome staining and secondary harmonic generation microscopy confirmed that MED12 mutant tumors are more fibrotic than MED12 wild-type tumors. Using shear-wave ultrasonography in a prospectively collected cohort, Black patients had fibroids that were firmer than White patients, even when similar in size. In addition, these analyses uncovered ancestry-linked expression quantitative trait loci with altered allele frequencies in African and European populations correlating with differential abundance of several proteins in uterine leiomyomas independently of MED12 mutation status, including tetratricopeptide repeat protein 38., Conclusion: Our study shows that Black women have a higher prevalence of uterine leiomyomas harboring mutations in MED12 and that this mutational status correlates with increased tissue fibrosis compared with wild-type uterine leiomyomas. Our study provides insights into molecular alterations correlating with racial disparities in uterine leiomyomas and improves our understanding of the molecular etiology underlying uterine leiomyoma development within these populations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common disease with several known extrarenal manifestations, although no known pulmonary features. The formation of renal cysts in ADPKD has been attributed to dysfunction of primary cilia and the primary cilia-related proteins polycystin-1 (in 85% of cases) and polycystin-2 in renal epithelial cells. The goals of this study were to characterize the normal expression of polycystin-1 in the motile cilia of airway epithelial cells and to evaluate lung structure in ADPKD patients., Methods: Airway epithelium from non-ADPKD patients was immunostained to localize polycystin-1 expression, and lung tissue from ADPKD patients was examined for pathologic changes. CT scans from ADPKD patients (n = 95) and a control group of non-ADPKD chronic kidney disease patients (n = 95) were retrospectively reviewed for the presence of bronchiectasis using defined criteria., Results: Immunostaining revealed polycystin-1 expression in the motile cilia of non-ADPKD airway epithelial cells. Lung tissue from one of five available ADPKD patient autopsies revealed histologic changes of bronchiectasis. Review of CT scans revealed a threefold-increased prevalence of bronchiectasis in the ADPKD group compared to the control group (37% vs 13%, p = 0.002)., Conclusions: ADPKD patients demonstrate an increased prevalence of radiographic bronchiectasis, a previously unrecognized manifestation of the disease. This association suggests that patients with primary cilia-associated diseases may be at risk for airway disease.