Uterine Fibroids in Senegal: Polymorphism of MED12 Gene and Correlation With Epidemiological Factors

Abstract

Background: Mediator complex subunit 12 (MED12) is a part of the mediator complex, which is believed to regulate transcription. Our recent study showed that MED12 is mutated at high frequency and with different mutation frequencies in Senegalese women with uterine fibroids. However, the status of mutations has not been correlated to the epidemiological factors that are implicated in uterine fibroids. Methods: This study aimed to analyze status of MED12 mutations in Senegalese population. MED12 was sequenced in tumoral tissues and blood samples of 54 Senegalese women with uterine fibroids. Clinical and pathological data were obtained from the patient’s records and other parameters were recorded. Mutation Surveyor software version 5.0.1, DnaSP version 5.10, MEGA version 7.0.26 and Arlequin version 3.5.1.3 were used to determine the level of mutations and genetics parameters. To estimate the genetic variation according to the epidemiological parameters, the index of genetic differentiation (Fst) and the genetic structure like analysis of molecular variance (AMOVA) were determined with Arlequin software version 3.5.1.3. The significance level (P-value) was 0.05. Results: Our results showed that MED12 is mutated at 88.89% (48/54) only in tumor tissues. The variants frequencies were not similar to those found in the Finnish populations. The Chi2 test indicates a statistically significant difference for the variants c.130G>C, c.130G>A, c.131G>A and for the Intronic Variant Site (p <0.05). This variable expression of the MED12 gene is further confirmed by the amino acid frequency between blood and tumor tissue with a statistically significant difference for alanine, glutamic acid, lysine, methionine, threonine, valine, tryptophan and tyrosine (p <0.05). In addition, the selection test indicates that codon 44 is under positive selection (p=0.0243) in cases of uterine fibroids. Genetic diversity according to risk factors such as parity and diet was observed in uterine fibroids in Senegal (p <0.05). Conclusion: Significant genetic diversity has been noted in uterine fibroids in Senegal. The codon 44 being under positive selection could be considered as a biomarker in uterine fibroids. Depending on the epidemiological parameters studied, parity and diet seem to be the risk factors most implicated in uterine fibroids in Senegal.