Polymorphisms of Glutathione S-Transferase mu-1 (GSTM1) and of Catechol-O-Methyltransferase (COMT) and risk of endometriosis

Abstract

Objective: Endometriosis affects 5–10% of reproductive-aged women in the US with chronic pain, dysmenorrhea, and infertility. Its etiology remains uncertain, but family history of endometriosis and exposures indicating high circulating estrogen levels are both associated with increased disease risk. GSTM1 is largely a detoxification enzyme that reduces xenobiotic toxicity by conjugating hydrophobic xenobiotics with glutathione to form hydrophilic and more readily excretable substances, and that also functions as an intracellular drug- and hormone-binding protein. GSTM1 appears in two active allele variants and one null-allele without mRNA or protein product. COMT is involved in the clearance of exogenous and endogenous estrogen via O-methylation. A transition of guanine to adenosine at nucleotide 544 of the COMT gene results in a change of amino acid 158 from valine (val) to methionine (met). The met/met (LL) and val/met (HL) COMT genotypes are associated, respectively, with low and intermediate levels of catechol substrate methylation relative to the val/val (HH)-genotype. The purpose of this study was to determine whether the risk of endometriosis is associated with the null GSTM1 genotype (GSTM1 0/0) or the low activity COMT genotype (COMT-LL).