Mutational Penetrance of the CYP17A1 Gene in the Evolution of Uterine Fibroids Coexisting with Pregnancy in Senegalese Women

Uterine fibroids, also known as myomas or leiomyomas, are the most common solid tumors of the gynecological tract. Symptoms associated with fibroids include excessive uterine bleeding, pelvic pain or pressure, infertility and pregnancy complications. It is not uncommon for fibroids to be diagnosed in pregnant women. They occur in between 3% and 12% of pregnant women, with some data indicating a prevalence of up to 20%. Our aim is to evaluate the evolution of uterine fibroids and to understand the genetic link between fibroids and pregnancy in Senegalese women. We used PCR-sequencing to analyze the impact of non-synonymous variants on the protein and variability of the CYP17A1 gene in 56 patients, including 20 pregnancy women with fibroids and 36 patients with fibroids only. First of all mutations were detected using Mutation Surveyor, then the pathogenicity of non-synonymous variants using in silicotools and the functional impact of non-synonymous variants were also analysed. The secondary and three-dimensional structure of the protein, gene/gene and protein/protein interactions were determined, and finally the sequences obtained were verified, cleaned and aligned. Molecular analyses of the gene showed that the c.-34 T>C polymorphism may be involved in the incidence of the disease and its progression during pregnancy. Five of the non-synonymous variants (p.Val5Gly, p.Ser30Asn, p.Gln57His, p.Val66Asp and p.Arg67His) are pathogenic. Six variants (p.Val5Gly, p.Leu8Val, p. Tyr14Asn, p.Phe16Ile, p.Lys26Thr) and one specific to fibroid tissue and pregnancy (p.Ser30Asn) create genetic disorders in the secondary structure. Co-expression with other genes and functional associations with other proteins are observed. The c.-34T>C polymorphism is involved in fibroid cell growth during pregnancy through the effect of hormone overexpression, while non-synonymous variants lead to dysfunction in protein synthesis and induce a change in the enzyme’s biological function.

Keywords: Fibroma, Pregnancy, In silico prediction, CYP17A1, Variability, Senegal.