Transcriptome and DNA methylome analyses reveal underlying mechanisms for the racial disparity in uterine fibroids

Document Type

Article

Publication Date

9-6-2022

Publication Title

JCI Insight

Abstract

Uterine fibroids (leiomyomas) affect Black women disproportionately in terms of prevalence, incidence, and severity of symptoms. The causes of this racial disparity are essentially unknown. We hypothesized that myometria of Black women are more susceptible to developing fibroids and examined the transcriptomic and DNA methylation profiles of myometria and fibroids from Black and White women for comparison. Myometrial samples cluster by race in both their transcriptome and DNA methylation profiles, whereas fibroid samples only cluster by race in the latter. More differentially expressed genes (DEGs) were detected in the Black and White myometrial sample comparison than in the fibroid comparison. Leiomyoma gene set expression analysis identified four clusters of DEGs, including a cluster of 24 genes with higher expression in myometrial samples from Black women. One of the DEGs in this group, VWF, was significantly hypomethylated at two CpG probes that are near a putative enhancer site in myometrial samples from Black women and in all fibroids and that correlate with VWF expression levels. These results suggest that the molecular basis for the disparity in fibroid disease between Black and White women could be found in the myometria before fibroid development and not in the fibroids themselves.

PubMed ID

36066972

ePublication

ePub ahead of print

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