Admixture mapping of uterine fibroid size and number in African American women

Abstract

Objective To evaluate the relationship between genetic ancestry and uterine fibroid characteristics. Design Cross-sectional study. Setting Not applicable. Patient(s) A total of six hundred and nine African American (AA) participants with image- or surgery-confirmed fibroids in the biorepository at Vanderbilt University (BioVU) electronic health record biorepository and the Coronary Artery Risk Development in Young Adults (CARDIA) studies were included. Intervention(s) None Main outcome Measure(s) Outcome measures include fibroid number (single vs multiple), volume of largest fibroid, and largest fibroid dimension of all fibroid measurements. Result(s) Global ancestry meta-analyses revealed a significant inverse association between percentage of European ancestry and risk of multiple fibroids (odds ratio [OR]: 0.78; 95% confidence interval [CI]: 0.66, 0.93; p = 6.05×10−3). Local ancestry meta-analyses revealed five suggestive (p<4.80×10−3) admixture mapping peaks in 2q14.3-2q21.1, 3p14.2-3p14.1, 7q32.2-7q33, 10q21.1, 14q24.2-14q24.3, for number of fibroids and one suggestive admixture mapping peak (p<1.97×10−3) in 10q24.1-10q24.32 for volume of largest fibroid. Single variant association meta-analyses of the strongest associated region from admixture mapping of fibroid number (10q21.1) revealed a strong association at (single nucleotide polymorphism) SNP variant rs12219990 (OR: 0.41; 95% CI: 0.28, 0.60; p = 3.82×10−6) that was significant after correction for multiple testing. Conclusion(s) Increasing African ancestry is associated with multiple fibroids but not fibroid size. Local ancestry analyses identified several novel genomic regions not previously associated with fibroid number and increasing volume. Future studies are needed to explore the genetic impact that ancestry plays into the development of fibroid characteristics.

Evidence that geographic variation in genetic ancestry associates with uterine fibroids

“…Further supporting this are ndings from our group that demonstrated that the frequency of broproliferative risk alleles varies by geographic ancestry with a much higher burden among African-ancestry populations and lower among European-derived populations (Hellwege et al, 2017). Admixture mapping analysis of broid risk and multiple broid risk also demonstrates increased risk among Black women compared to White women (Bray et al, 2017, Giri et al, 2017.…”

Uterine Weight as a Modifier of Black/White Racial Disparities in Minimally Invasive Hysterectomy Among Veterans with Fibroids in the Veterans Health Administration

“…Our finding that black Veterans with UF were more likely than white Veterans with UF to have larger uterine size is consistent with prior literature. 41 Previously, Kjerulff et al reported that, compared with white women undergoing hysterectomy for UF, black women had ∼100 g larger mean postoperative uterine weight (420.8 g vs. 319.1 g). 42 Prospective data also indicate that black people experience earlier onset of fibroids and larger and more numerous fibroids than their white counterparts.…”

“…However, these differences in UF cannot be explained by genetic variations in socially constructed racial categories. 41 , 44 …”

A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity

“…Furthermore, so-called “protective” single-nucleotide variants, which reduce UL risk, have been discovered in the introns of the following genes: KCNMB2 (potassium calcium-activated channel subfamily M regulatory beta subunit 2), FBN2 (fibrillin 2), ESR1 (oestrogen receptor 1) and CELF4 (CUGBP Elav-like family member 4) [ 82 ]. Researchers have also described COL6A3 (collagen type VI alpha 3 chain), COL13A (collagen type XIII alpha 1 chain), ARHGAP26 (Rho GTPase activating protein 26), MAN1C1 (mannosidase alpha class 1C member 1), BET1L (Bet1 golgi vesicular membrane trafficking protein like), TNRC6B (trinucleotide repeat containing adaptor 6B) and COMT (catechol-O-methyltransferase) gene variants associated with the accumulation of ECM in the UL tissue, the size, localisation and the multiple form of UL [ 83 , 84 , 85 , 86 , 87 ].…”