Transcriptome and DNA methylome analyses reveal underlying mechanisms for the racial disparity in uterine fibroids.
Transcriptome and DNA methylome analyses reveal underlying mechanisms for the racial disparity in uterine fibroids.
复制标题
DOI：
10.1172/jci.insight.160274
复制
发表时间：
2022-10-24
期刊：
影响因子：
8
通讯作者：
Teixeira, Jose M.
中科院分区：
文献类型：
--
作者：
Paul, Emmanuel N.;Grey, Joshua A.;Carpenter, Tyler J.;Madaj, Zachary B.;Lau, Kin H.;Givan, Scott A.;Burns, Gregory W.;Chandler, Ronald L.;Wegienka, Ganesa R.;Shen, Hui;Teixeira, Jose M.
子宫肌瘤（平滑肌瘤）在患病率、发病率和症状严重程度方面与其他种族和民族的妇女相比，对黑人妇女的影响不成比例。这种种族差异的原因基本上是未知的。我们假设黑人妇女的子宫肌层更容易发生肌瘤，我们检查了黑人和白色妇女子宫肌层和肌瘤的转录组和DNA甲基化谱进行比较。子宫肌层样本在转录组和DNA甲基化图谱中按种族聚类，而子宫肌瘤样本仅在后者中按种族聚类。在黑色和白色子宫肌层样本比较中检测到的差异表达基因（DEG）比在肌瘤比较中检测到的差异表达基因更多。平滑肌瘤基因集表达分析鉴定了4个DEG簇，包括在来自黑人妇女的子宫肌层样品中具有较高表达的24个基因的簇。该组中的DEG之一，von Willibrands因子（VWF），在来自黑人妇女的子宫肌层样品和所有肌瘤中在2个CpG探针处显著低甲基化，所述探针靠近推定的增强子位点并且与VWF表达水平相关。这些结果表明，黑人和白色妇女之间纤维瘤疾病差异的分子基础可能是在纤维瘤发展之前的子宫肌层中，而不是在纤维瘤本身中。
Uterine fibroids (leiomyomas) affect Black women disproportionately compared with women of other races and ethnicities 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 we 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 4 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, von Willibrands factor (VWF), was significantly hypomethylated in both myometrial samples from Black women and in all fibroids at 2 CpG probes that are near a putative enhancer site and that are correlated 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.
登录
查看更多内容
影响因子：
13.3
作者：
Donnez J;Dolmans MM
通讯作者：
Dolmans MM
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1093/database/bax028
发表时间：
2017-01-01
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Fishilevich S;Nudel R;Rappaport N;Hadar R;Plaschkes I;Iny Stein T;Rosen N;Kohn A;Twik M;Safran M;Lancet D;Cohen D
通讯作者：
Cohen D
影响因子：
6
作者：
Hu, Biao;Gharaee-Kermani, Mehrnaz;Phan, Sem H.
通讯作者：
Phan, Sem H.
影响因子：
3.6
作者：
Halder, Sunil K.;Sharan, Chakradhari;Al-Hendy, Ayman
通讯作者：
Al-Hendy, Ayman