AUTHOR=Kénémé Bineta , Sembène Mbacké 

TITLE=GTn Repeat Microsatellite Instability in Uterine Fibroids

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00810

DOI=10.3389/fgene.2019.00810

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold><italic>Type I collagen</italic> is a triple helix structure with two α1 and one α2 chains. Coordinated biosynthesis of α1 and α2 subunits is very important for tissue morphogenesis, growth, and repair. In contrast, abnormal deposition in response to proinflammatory cytokines is associated with organ dysfunction. In humans, <italic>COL1A2</italic> contains two microsatellite loci: one located at the 5’-flanking region is composed of poly CA and poly CG; the other located in the 1st intron is constituted of poly GT. Expression of <italic>COL1A2</italic> has been noted in gastric cancer and was positively correlated with degree of invasion and metastases. But no genetic study taking into account polymorphism of <italic>COL1A2</italic> in uterine fibroids has been undertaken.</p><p><bold>Methods:</bold> In this study, repeated dinucleotide <bold>GT</bold><bold><sub>n</sub></bold> of intron 1 <bold><italic>COL1A2</italic></bold> was highlighted in 55 patients with uterine fibroids (UF). Clinical and pathological data were obtained from patient’s records, and other parameters were recorded. Mutation Surveyor version 5.0.1, DnaSP version 5.10, MEGA version 7.0.26, and Arlequin version 3.5.1.3 were used to determine genetics parameters. To estimate genetic variation according to epidemiological parameters, index of genetic differentiation (Fst) and genetic structure (AMOVA) were determined with Arlequin version.</p><p><bold>Results:</bold> Based on reference microsatellite pattern <bold>(GT)</bold><bold><sub>14</sub></bold><bold>CT(GT)</bold><bold><sub>3</sub></bold><bold>CT(GT)</bold><bold><sub>3</sub></bold>, 15 haplotypes were found. Among the 15 haplotypes, 12 have mutation at position <bold>2284C &gt; G</bold> and 7 at position <bold>2292C &gt; G</bold>. Insertions of repeated dinucleotide GT<sub>n</sub> were found on three haplotypes against eight haplotypes in which they are deletions. Intron 1 of <italic>COL1A2</italic> gene exhibits high genetic diversity in uterine fibroids with 35.34% polymorphic sites, 95.74% of which were parsimoniously variable and an average number of nucleotide difference of 10.442, which reflects an important genetic variability. According to epidemiological parameters, our results showed, for the first time, a genetic structuring of uterine fibroids according to ethnicity, marital status, use of contraception, diet, and physical activity, beyond confirming the involvement dinucleotide length polymorphism GT<sub>n</sub> in occurrence of uterine fibroids in Senegalese women.</p><p><bold>Conclusion:</bold> Results obtained open up avenues for understanding the mechanisms involved in the racial variation in the prevalence of uterine fibroids as well as the predisposing factors.</p>