{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:29:44Z","timestamp":1791286184053,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["R01CA254367"],"award-info":[{"award-number":["R01CA254367"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"NICHD","doi-asserted-by":"publisher","award":["P01HD057877"],"award-info":[{"award-number":["P01HD057877"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,3]]},"abstract":"Abstract<\/jats:title>STUDY QUESTION<\/jats:title>Are there differences in Mediator Complex Subunit 12 mutations (MED12) mutation, transcriptomics, and protein expression in uterine myometrium and leiomyomas of Black and White women?<\/jats:p><\/jats:sec>SUMMARY ANSWER<\/jats:title>RNA sequencing, tissue microarray, and immunohistochemistry data revealed that Black and White women have significant differences in their myometrium and leiomyoma profiles.<\/jats:p><\/jats:sec>WHAT IS KNOWN ALREADY<\/jats:title>Black women develop uterine leiomyoma earlier than White women, and are more likely to be anemic, have multiple tumors, undergo hysterectomy at an earlier age, have a higher uterine weight, and report very severe pelvic pain.<\/jats:p><\/jats:sec>STUDY DESIGN, SIZE, DURATION<\/jats:title>Uterine tissues were collected from premenopausal women undergoing hysterectomy or myomectomy at Northwestern University Prentice Women\u2019s Hospital (Chicago, IL) from 2010 to 2021. Tissues were collected from a total of 309 women, including from 136 Black women, 135 White women, and 38 women from other racial groups. A total of 529 uterine leiomyomas (290 from Black women, 184 from White women, and 55 from women of other racial groups) were subjected to molecular analysis. Leiomyoma and matched myometrium from a total of 118 cases including 60 Black women and 58 White women, were used for tissue microarrays, along with 34 samples of myometrium without leiomyoma from White women.<\/jats:p><\/jats:sec>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>Tissues from the above patient cohorts were analyzed by tissue microarray, immunohistochemistry, RNA sequencing, and mutation analysis.<\/jats:p><\/jats:sec>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>The results indicated that leiomyoma from Black women have a higher rate of MED12 mutations (79.0%) than those from White women (68.5%) (*P\u2009\u2264\u20090.05). RNA-sequencing analysis in myometrium revealed differentially expressed genes (270 upregulated, 374 downregulated) dependent on race, wherein reactive oxygen species, hypoxia, and oxidative phosphorylation pathways were positively correlated with samples derived from Black patients. The levels of proteins associated with oxidative DNA damage and repair, 8-hydroxyguanosine (8-OHdG), 8-oxoguanine glycosylase (OGG1), heme oxygenase-1 (HO-1), and kelch-like ECH-associated protein 1 (KEAP1), were higher in leiomyoma and matched myometrium, particularly those from Black patients, compared to the control myometrium (with leiomyoma) (***P\u2009\u2264\u20090.001).<\/jats:p><\/jats:sec>LARGE SCALE DATA<\/jats:title>The datasets are available in the NCBI (The BioProject number: PRJNA859428).<\/jats:p><\/jats:sec>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>Myometrium without leiomyoma derived from White patients was used as a control in the tissue microarray analysis, as myometrium without leiomyoma from Black patients was not accessible in large numbers. The RNA sequencing was performed on myometrium tissue with leiomyoma present from 10 White and 10 Black women. However, one sample from a Black woman yielded low-quality RNA-sequencing data and was excluded from further analysis.<\/jats:p><\/jats:sec>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>Women with symptomatic leiomyomas have a considerable loss in their quality of life. This study provides information on underlying genetic and molecular defects that may be necessary for future therapeutics targeted at leiomyomas.<\/jats:p><\/jats:sec>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>This work was supported by grants from NCI (R01CA254367) and NICHD (P01HD057877). The authors declare no conflict of interest.<\/jats:p><\/jats:sec>","DOI":"10.1093\/humrep\/dead020","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T19:53:00Z","timestamp":1675799580000},"page":"609-620","source":"Crossref","is-referenced-by-count":16,"title":["Racial differences in transcriptomics and reactive oxygen species burden in myometrium and leiomyoma"],"prefix":"10.1093","volume":"38","author":[{"given":"Yinuo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology, Northwestern University , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9244-8683","authenticated-orcid":false,"given":"Ross P","family":"McNally","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Northwestern University , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9834-8213","authenticated-orcid":false,"given":"J Julie","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Northwestern University , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-2793","authenticated-orcid":false,"given":"Jian-Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University , Chicago, IL, USA"},{"name":"Department of Obstetrics and Gynecology, Northwestern University , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1067\/mob.2003.99","article-title":"High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence","volume":"188","author":"Baird","year":"2003","journal-title":"Am J Obstet Gynecol"},{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/modpathol.2013.243","article-title":"MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma","volume":"27","author":"Bertsch","year":"2014","journal-title":"Mod Pathol"},{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1038\/oby.2008.657","article-title":"Impact of race\/ethnicity on the relationship between visceral fat and inflammatory biomarkers","volume":"17","author":"Carroll","year":"2009","journal-title":"Obesity (Silver Spring)"},{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/j.1471-0528.1999.tb08409.x","article-title":"Use of oral contraceptives and uterine fibroids: results from a case-control study","volume":"106","author":"Chiaffarino","year":"1999","journal-title":"Br J Obstet Gynaecol"},{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/humupd\/dmv030","article-title":"Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth","volume":"21","author":"Commandeur","year":"2015","journal-title":"Hum Reprod Update"},{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1752-8062.2011.00264.x","article-title":"Racial differences in oxidative stress and inflammation: in vitro and in vivo","volume":"4","author":"Feairheller","year":"2011","journal-title":"Clin Transl Sci"},{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1016\/j.ajpath.2018.06.023","article-title":"Expanding upon the human myometrial stem cell hypothesis and the role of race, hormones, age, and parity in a profibroid environment","volume":"188","author":"Fernung","year":"2018","journal-title":"Am J Pathol"},{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.jvs.2014.02.045","article-title":"Gender and racial differences in endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease","volume":"61","author":"Gardner","year":"2015","journal-title":"J Vasc Surg"},{"key":"2023040319425671400_","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s43032-021-00473-x","article-title":"Frequency of MED12 mutation in relation to tumor and patient\u2019s clinical characteristics: a meta-analysis","volume":"29","author":"He","year":"2022","journal-title":"Reprod Sci"},{"key":"2023040319425671400_","first-page":"483","article-title":"Uterine leiomyomas. 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