Gene Polymorphisms Determining Sex Hormone-Binding Globulin Levels and Endometriosis Risk

Area of Science:

• Genetics
• Endocrinology
• Reproductive Medicine

Background:

• Endometriosis is a complex, hormone-dependent disease.
• Sex hormones, particularly androgens and estrogens, play a crucial role in its pathophysiology.
• Sex hormone-binding globulin (SHBG) influences the bioavailability of these hormones, potentially impacting endometriosis risk.

Purpose of the Study:

• To investigate the association between genetic determinants (SNPs) of SHBG and endometriosis risk in Caucasian Russian women.
• To identify specific SHBG-related genetic loci and their interactions contributing to endometriosis development.

Main Methods:

• Genome-wide associative studies (GWAS) data were used to select nine SHBG-influencing loci.
• A case-control study involving 1368 women (395 with endometriosis, 973 controls) was conducted.
• Statistical analyses evaluated independent and interacting effects of SNPs, including in silico pathway analysis.

Main Results:

• The polymorphic locus rs440837 (A > G) in the ZBTB10 gene was significantly associated with endometriosis risk under a recessive model.
• The GG genotype at rs440837, which increases SHBG levels, nearly doubled the risk of endometriosis (OR = 1.91).
• Interactions between seven SHBG-influencing SNPs and their association with endometriosis were identified.

Conclusions:

• Polymorphic variants impacting SHBG levels are associated with an increased risk of endometriosis.
• The rs440837 SNP in ZBTB10 is a significant risk factor for endometriosis, likely through its effect on SHBG.
• These findings underscore the importance of SHBG-related genetic factors in endometriosis pathophysiology.