Obesity/Overweight as a Meaningful Modifier of Associations Between Gene Polymorphisms Affecting the Sex...

The main goal of this study was to consider the role of obesity/overweight as a potential modifier of associations between gene single nucleotide polymorphisms (SNPs) affecting the sex hormone-binding globulin level (SHBG_level) and uterine myoma (UM). In the two women cohorts differentiated by body mass index (BMI) (BMI ≥ 25, n = 782 [379 UM/403 control] and BMI < 25, n = 760 [190 UM/570 control]), the association of genome-wide association studies (GWAS)-correlated SHBG_level-tied nine loci with UM was studied by method logistic regression with a subsequent in-depth evaluation of the functionality of UM-causal loci and their strongly linked variants. BMI-conditioned differences in the associations of SHBG_level-tied loci with UM were revealed: in the BMI < 25 group, a variant rs17496332 (A/G) PRMT6 was UM-correlated (OR = 0.70; p_perm = 0.024), and in the BMI ≥ 25 cohort, a SNP rs3779195 (T/A) BAIAP2L1 was UM-associated (OR = 1.53; p_perm = 0.019). Both the UM-causal loci and their proxy SNPs have pronounced probable functionality in the organism as a whole, as well as in the liver (the SHBG synthesis place), adipose tissue, uterus, etc., thereby influencing significant processes for UM biology such as regulation of the gene transcription, embryogenesis/development, cell proliferation/differentiation/apoptosis, metabolism, lipid exchange, etc. In conclusion, the results of our work demonstrated, for the first time, the essential role of obesity/overweight as a meaningful modifier of associations between SHBG_level-tied polymorphisms and UM.