BMI-Dependent Correlations of Sex Hormone Genes with Simple Endometrial Hyperplasia

The aim of the work was to identify the features of associations of single nucleotide polymorphisms (SNPs) that determine the level of sex hormones in the body with simple endometrial hyperplasia without atypia (EnH_s) in women with different body mass index (BMI). Two groups of BMI-differing subjects (BMI < 25 [n = 766]: 196 EnH_s, 570 control and BMI ≥ 25 [n = 727]: 324 EnH_s, 403 control) with a total number of 1493 women were formed to conduct this study. Nine SNPs meaningful for the level of sex hormones (proven in genome-wide association studies [GWAS]) such as rs34670419 [G>T] ZKSCAN5, rs148982377 [T>C] ZNF789, rs11031002 [T>A] FSHB, rs11031005 [T>C] FSHB, rs112295236 [C>G] SLC22A10, rs117145500 [A>C] CHD9, rs727428 [C>T] SHBG, rs1641549 [C>T] TP53, rs117585797 [C>A] ANO2 were considered by us. In general, in the studied sample (EnH_s/control, n = 1493), an association of interactions of rs148982377 [T>C] ZNF789 × BMI with EnH_s (OR = 1.11) was revealed. As a result of a comparative analysis, we found that rs148982377 [T>C] ZNF789 was associated with EnH_s in women with a BMI ≥ 25 (OR = 1.77) and was not linked with the disease in women with a BMI < 25. Both common protective factors for EnH_s were also identified in women with BMI ≥ 25 and BMI < 25 (rs11031002 [T>A] FSHB (OR = 0.43 and OR = 0.46 respectively) and rs11031005 [T>C] FSHB (OR = 0.46 and OR = 0.58 respectively)). At the same time, in the BMI ≥ 25 cohort, the risk effect of the TT*rs11031002-rs11031005 haplotype (OR = 3.27) was more pronounced, and the contribution of interlocus interactions of sex hormone genes with EnH_s formation was more significant (7 SNPs in 12 models) than in the BMI < 25 group (OR = 2.31 and 4 SNPs in 3 models). In conclusion, the presented work is exploratory and demonstrates differences in the nature of the association with EnH_s in women with different BMI of the testosterone-determining polymorphism: SNP rs148982377 [T>C] ZNF789 was associated with EnH_s in women with a BMI ≥ 25 and was not linked with the disease in women with a BMI < 25.