Fibrosis Severity and Pro-fibrotic Gene Expression in Uterine Leiomyomas: Relationship with Self-reported Skin Color/Race and Genomic Ancestry

子宫平滑肌瘤纤维化严重程度和促纤维化基因表达:与自我报告的肤色/种族和基因组祖先的关系

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Abstract

Uterine leiomyomas (ULM) are highly prevalent benign gynecologic tumors and the leading indication for hysterectomy. Black women experience a disproportionate impact of ULMs compared to White women, but the mechanisms underlying this racial disparity remain elusive. The aim of this study was to evaluate the degree of fibrosis and the expression of pro-fibrotic genes in ULMs from Brazilian women according to self-reported color/race and genomic ancestry. Study participants (n = 30) were divided into three groups (n = 10) according to self-declared skin color/race: Black, Brown, or White. ULM tissue was collected through hysterectomy. Fibrosis was quantified by Masson's trichrome staining and the expression of pro-fibrotic genes COL1A1 (type 1 collagen), FN1 (fibronectin 1) and VCAN (versican) was assessed by qPCR. The genetic ancestry was determined by typing DNA for a panel of 40 validated ancestry-informative biallelic short insertion/ deletion DNA polymorphisms. The three groups presented homogeneous clinical and demographic data. The proportion of fibrotic tissue in the ULM histological sections was similar in the three groups. The mRNA levels of type 1 collagen were lower in Black than in Brown group (p < 0.05) while fibronectin and versican expression did not change according to self-reported color. There was no correlation between fibrosis or pro-fibrotic gene expression and the proportion of European, African or Amerindian genomic ancestry of the participants. These findings suggest that differences in the amount of fibrosis or the expression of pro-fibrotic genes by the time of hysterectomy are unlikely to explain racial disparities in the burden of uterine leiomyomas among Brazilian women.

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