Folate Metabolism Abnormalities in Infertile Patients with Endometriosis

Abstract

Background: Homocysteine levels can be impacted by enzymes variations. Aim: To correlate MTHFR, MTR and MTRR variants with homocysteine levels in the blood and follicular fluid and assisted reproduction results. Material & methods: MTHFR (rs2274976, rs1801131, rs1801133), MTR (rs1805087) and MTRR (rs1801394) genotyping was performed by TaqMan assays and compared with homocysteine levels, measured by ELISA, to oocytes retrieved and to the pregnancy status of women with endometriosis and controls. Results: The MTR G allele and GG genotype were more common in patients with endometriosis. They also showed lower levels of homocysteine and more clinical gestations. Epistasis analysis showed a model associated with gestational results, composed of MTHFR+MTR variants (CC+AG). Conclusion: The summation effect of variants in genes participating in folate metabolism was associated with pregnancy status in Brazilian women. MTR variants were more observed in endometriosis patients, as well as lower follicular Hcy levels and increased clinical pregnancy results.

Homozygous C677T Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism as a Risk Factor for Endometriosis: A Retrospective Case–Control Study

“…On the other hand, Guedes et al conducted a study on 61 infertile patients with endometriosis and 91 infertile controls in 2022. The authors found no difference in MTHFR allele frequency between cases and controls, and a higher frequency of methionine synthase (MTR gene) G allele and GG genotype, as well as an association at the epistasis analysis of the combination between MTHFR and MTR variants (CC+AG) and pregnancy rate [16]. However, the reported studies focus only on infertile patients with endometriosis and did not account for potential confounders in the association between MTHFR polymorphisms and endometriosis.…”

“…Aberrant DNA methylation has been reported in endometriotic tissue in genes implicated in the hormonal and inflammatory factors of endometriosis pathogenesis (estrogen and progesterone receptors ERα, Erβ, and Prβ, the aromatase CYP19, the homebox protein HOXA-10, and the cyclooxygenase COX-2) [7][8][9][10][11]14]. Moreover, there is preliminary evidence about the association between MTHFR polymorphisms, endometriosis, and endometriosis-related infertility [15][16][17]. Therefore, it is possible to hypothesize that MTHFR polymorphisms may act as one of the risk factors for endometriosis, supporting mechanisms of aberrant DNA methylation in critical genes of endometriosis pathogenesis.…”

“…Moreover, there is preliminary evidence about the association between MTHFR polymorphisms, endometriosis, and endometriosis-related infertility [15][16][17]. Therefore, it is possible to hypothesize that MTHFR polymorphisms may act as one of the risk factors for endometriosis, supporting mechanisms of aberrant DNA methylation in critical genes of endometriosis pathogenesis.…”

Pre-pregnancy training of women with early pregnancy loss and adenomyosis, taking into account folate cycle gene polymorphisms

“…Гіпергомоцистеїнемія, що триває протягом всієї вагітності, справляє безумовний токсичний вплив на судинну стінку, що супроводжується підвищеним ризиком тромбоутворення та розвитку відповідних гестаційних ускладнень [11][12][13]. Крім того, низка досліджень засвідчила наявність асоціації між поліморфізмом генів фолатного циклу та підвищенням ризику виникнення таких хромосомних аномалій, як синдроми Дауна й Едвардса [14].…”

“…Літературні джерела також містять інформацію про те, що у жінок з ендометріозом та репродуктивною дисфункцією спостерігається поліморфізм генів фолатного обміну та порушення метаболізму фолатів [11].…”