Single nucleotide polymorphism of the SLC22A10 gene and the risk of endometrial hyperplasia

Objective. To evaluate the association of a single nucleotide polymorphism (SNP) associated with sex hormone levels with the risk of endometrial hyperplasia (EH) in women with normal body weight. Material and methods. The study was conducted on a sample of 766 women (196 patients with EH and 570 in the comparison group) with a body mass index (BMI) <25 kg/m². Genotyping of four polymorphisms (rs34670419 G>T ZKSCAN5, rs1641549 C>T TP53, rs148982377 T>C ZNF789, rs112295236 C>G SLC22A10) associated with sex hormone levels according to genome-wide association studies (GWAS) data was performed. The association of polymorphisms with EH was assessed by regression analysis. Results. The rs112295236 C>G SLC22A10 polymorphism was associated with EH according to the dominant model (OR 1.74; 95% CI 1.01—3.02; pperm=0.050). The presence of the alternative G variant rs112295236 SLC22A10 (genotypes GG+CG) in a woman’s genotype increases her risk of developing the disease (OR > 1). Using an in silico approach, it was shown that the rs112295236 SLC22A10 variant and 65 strongly linked loci may be functionally significant in relation to five genes: SLC22A24, SLC22A25 (epigenetic modifications), SLC22A9, ATL3 (expression), and SLC22A10 (epigenetic modifications and expression). Conclusion. The rs112295236 C>G polymorphism in SLC22A10 is associated with EH in women with normal body weight, which may be used in the future to diagnose (prognosticate) EH in women with normal body weight.