Implication of <I>CYP17A1</I> Gene Mutations in the Association of Fibroma and Pregnancy in Senegalese Women

Abstract

<i>Background. </i>Uterine fibroids are the most common gynaecological tumours and represent a significant medical and financial burden. Several genetic, hormonal and biological factors have been shown to contribute to the development and growth of these tumors.<i> Objective.</i> We aimed to evaluate the evolution of fibroma during pregnancy and understand the genetic link between fibroma and pregnancy in Senegalese women.<i> Methods.</i> We analyzed the functional impact of non-synonymous variants on the CYP17A1 protein in 20 pregnant patients with fibroids, using PCR-sequencing. First of all, mutations were detected using Mutation Surveyor, then the functional impact of non-synonymous variants was analysed using In Silico tools, the secondary and three-dimensional structure of the protein were also analysed. After, raw data were aligned using BioEdit software for doing phylogenetic analysis. <i>Results.</i> The results show that the <I>CYP17A1</I> gene is involved in the development of uterine fibroids in pregnant women, and that the c.-34T>C polymorphism plays an important role; on the one hand, some of non-synonymous mutations (p.Lys26Thr and p.Ser30Asn) have caused genetic disorders on the secondary structure, and on the other, others (p.Lys26Thr, p.Ser30Asn and p.Ser39Asn) have destabilizing effects on the protein.<i> Conclusion.</i> 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. The c.76A>T (p.Lys26*) mutation results in a truncated CYP17A1 protein, and cause premature loss of function. The non-synonymous variants (p.Lys26Thr, p.Ser30Asn and p.Ser39Asn) induce a change in the enzyme's biological function.