Polymorphic Variant Associated with Sex Hormone-Binding Globulin Level Is a Risk Factor for Preeclampsia.

The present study was devoted to the analysis of associations of single-nucleotide polymorphisms (SNPs) of genes affecting the concentration of circulating sex hormone-binding globulin (SHBG) (information was obtained from genome-wide association studies [GWAS]) with the development of preeclampsia (PE). This retrospective study was performed with a case-control design using a sample of 891 pregnant women, including women with PE [n = 431] and without PE (control) [n = 460] who underwent an experimental genetic study of 11 SNPs (rs17496332 [PRMT6], rs780093 [GCKR], rs10454142 [PPP1R21/KLRAQ1], rs3779195 [BAIAP2L1], rs440837 [ZBTB10], rs7910927 [JMJD1C], rs4149056 [SLCO1B1], rs8023580 [NR2F2-AS1], rs12150660 [SHBG], rs727428 [SHBG], and rs1641549 [TP53]) that had previously shown a connection with the concentration of circulating SHBG in GWAS. As a result of the associative analysis, it was revealed that the polymorphism rs10454142 PPP1R21/KLRAQ1 was associated with PE risk [the data were obtained within the framework of a recessive genetic model]: the CC genotype of this SNP had an impact risk value for PE (OR: 1.73; 95%CI: 1.16-2.66; pperm: 0.014). The PE-associated variant rs10454142 PPP1R21/KLRAQ1 and its proxy SNPs demonstrate potential pronounced functionality both in the liver (the main organ of SHBG formation) and organs/cell cultures targeted for PE (trophoblast, amnion, placenta, and uterus), thereby affecting the regulation of gene transcription, nucleic acid metabolism, and embryo development. In conclusion, this exploratory study was the first to show the risk effect of the SHBG-related genetic variant in the formation of PE.