Genetic Variation of Glutathione S-Transferase M1 Is Associated with Patients with Ovarian Endometriosis and Endometriosis-Related Primary Infertility

Abstract

<b><i>Background:</i></b> The aim of the study was to investigate the role of the genetic variation of glutathione S-transferase M1 (<i>GSTM1</i>) in the development of ovarian endometriosis and endometriosis-related primary infertility risk. <b><i>Methods:</i></b> This case-control study included 564 women with ovarian endometriosis and 576 normal women in the control group in northern China. The polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR)/ligase detection reaction method. To assess the biological significance of polymorphisms, the level of GSTM1 mRNA expression in patients’ endometrial tissues with different genotypes was detected by quantitative real-time PCR (qRT-PCR). <b><i>Results:</i></b> Compared with the positive genotype, the null genotype of <i>GSTM1</i> was associated with the risk of developing ovarian endometriosis (OR = 1.29, 95% CI = 1.02–1.62). Further analysis showed that patients with a null genotype also had a significantly higher risk of primary infertility than patients with positive genotypes (OR = 1.59, 95% CI = 1.01–2.49). In addition, we found that <i>GSTM1</i> mRNA expression was present in the endometrial tissue of all patients, but the expression level of patients with a positive genotype was nearly 10 times higher than that of patients with a negative genotype. <b><i>Conclusion:</i></b> Our results suggest that the <i>GSTM1</i> polymorphism is not only related to the genetic susceptibility to ovarian endometriosis but also a potential molecular marker of primary infertility in patients with ovarian endometriosis.

Detection of GSTM1-null Genotype in Women Undergoing IVF Treatment

“…Oxidative stress involvement in unexplained infertility and endometriosis has been previously supported [29]. Zhang et al demonstrated that the GSTM1-null genotype is an independent risk factor for the development of endometriosis, and it is involved in primary infertility [13]. Mavrogianni et al revealed that the absence of GSTM1 gene detected in women with endometriosis, may indicate a possible involvement of the detoxifying metabolic pathway in the pathophysiology of the disease.…”

“…Like the other members of the glutathione-S-transferases family, GSTM1 act also as a hormone binding protein. The corresponding encoding sequence is well recognized for its high polymorphism [13][14][15]. Due to an extended deletion of the gene (approximately 10 kb), a null activity allele is produced, leading to a non-functional protein [4,12,16].…”