In Silico Study of the Functional Effects of TNRC6B Polymorphic Loci Associated with the Risk of Developing Uterine Leiomyomas According to Genome-Wide Studies †

Abstract

: Uterine leiomyoma (UL) is the most common benign tumor causing considerable morbidity during the reproductive years in women with contributions from environmental and genetic factors. According to the GWAS studies, there are many genes and polymorphisms that are related with and are somehow responsible for the UL pathogenesis, but the biological mechanisms underlying this association remain unclear. This study aimed to investigate the published GWAS studies of UL to recognize the significant functionality of TNRC6B polymorphism linked with UL. Six SNPs were selected based on the seven GWAS published on their association with UL by PubMed database. For their analyses, including their epigenetic effects, expression and splicing patterns, we used in silico approach and bioinformatics tools (HaploReg, GTEx-portal and Gene Ontology Resource). Based on HaploReg, several epigenetic effects regulating these SNPs were found as: rs12484776 (one motif changed, sixteen enhancers and four DNAs histone markers), rs4821939 (three motifs changed, eleven enhancers, four protein bounds and five DNAs histone markers), rs733381 (two motifs changed, eleven enhancers, one protein bound and two DNAs histone markers), rs12484951 (one motif changed histone markers), rs3830738 (five motifs changed histone markers) and rs17332320 (two motifs changed and two DNAs histone markers). Based on on GTEx, it was inferred that rs12484776, rs4821939, rs733381, rs3830738, rs12484951 and rs17332320 are associated with the expression of genes/in tissues as 4/4, 4/4, 4/4, 3/3, 4/4 and 2/2, respectively. These loci do not regulate the expression level of any genes in the UL pathophysiology important tissues, and are not associated with the alternative splicing traits (sQTL) of any gene in any tissue. Gene Ontology Resource indicated that no statistically significant biological pathways for genes associated with the studied polymorphisms have been identified. The in silico analysis of GWAS TNRC6B gene polymorphisms significant for fibroids have pronounced epigenetic effects and affect the expression of six genes ( RP51042K10.10 , FAM83F , TNRC6B , RP51042K10.13 , SLC25A17 and XPNPEP3 ), which may be the basis of their involvement in the pathophysiology of fibroids.