Familial Predisposition to Leiomyomata: Searching for Protective Genetic Factors

Abstract

In order to determine genetic loci associated with decreasing risk of uterine leiomyomata (UL), a genome-wide association study (GWAS) was performed. We analyzed a group of patients with a family history of UL and a control group consisting of patients without uterine fibroids and a family predisposition to this pathology. Six significant single nucleotide polymorphisms were selected for PCR-genotyping of a large data set of patients with UL. All investigated loci (rs3020434, rs11742635, rs124577644, rs12637801, rs2861221, and rs17677069) demonstrated the lower frequency of minor alleles within a group of women with UL, especially in a subgroup consisting of patients with UL and a familial history of leiomyomata. We also found that the minor allele frequencies of these SNPs in our control group were higher than those across the Caucasian population in all. Based on the obtained data, an evaluation of the common risk of UL was performed. Further work will pave the way to create a specific SNP-panel and allow us to estimate a genotype-based leiomyoma incidence risk. Subsequent studies of genetic variability in a group of patients with a familial predisposition to UL will allow us to make the prediction of the development and course of the disease more individualized, as well as to give our patients personalized recommendations about individual reproductive strategies.

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

“…These genes are involved in DNA damage repair, telomere length maintenance, hormonal and paracrine regulation, apoptosis, urogenital system development and early menarche. 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 ].…”

Uterine Artery Embolization for the Treatment of Symptomatic Uterine Fibroids of Different Sizes: A Single Center Experience

“…Fibroids are more common, tend to present at a younger age, and are greater in number and larger in size in women of African ancestry versus White or Asian women [ 5 ]. Women may develop both solitary and multiple uterine fibroids, but the prevalence of the latter is higher [ 6 ].…”