Endometriosis and RAS System Gene Polymorphisms: The Association of ACE A2350G Polymorphism with Endometriosis in Polish Individuals

Abstract

To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

Is M235T polymorphism of the angiotensinogen gene involved in the development of endometriosis?

“…According to the authors, allele I both in homo-(II) and heterozygous (ID) systems increased the risk of endometriosis. Different results were obtained by the authors of this paper in their previous studies [22]. The study included 241 women with endometriosis (I-IV).…”

“…Whereas in the case of ACE A2350G polymorphism G allele and AG genotype but not GG, occurred significantly more frequently in the study group than in the control group (p < 0.0001). However, there were no differences in the frequency of individual alleles and genotypes between the different stages of the disease progression or between stage I and II and III and IV [22]. Hsieh et al also observed that ACE A2350G gene polymorphism was associated with higher susceptibility to moderate/severe endometriosis in the Asian population [23].…”

Involvement of angiotensin II receptor type 1/NF‑κB signaling in the development of endometriosis

“…Notably, the dysregulation of the RAS has been observed in EM; for example, Abraham et al (26) reported that, in rat endometrial stromal cells, AngII induced Cyclooxygenase-2 gene expression by activating the calcineurin/NFAT signaling pathway. In another study, Kowalczyńska et al (27) investigated the polymorphisms in the angiotensin I converting enzyme (ACE) gene and AGTR1 in women with EM, and their results indicated that the A2350G polymorphism in the ACE gene was associated with the development of EM. Nakao et al (28) discovered that the expression of AGTR1 was largely located in endometrial glandular epithelium and stromal cells, and AGTR1 expression levels were markedly increased in EM compared with those of normal tissue.…”

“…The collected tissues were histologically confirmed by pathologists. Data concerning the patients' menstrual cycle phases were collected by ZZ, YY and LH, and were classified into the proliferative phase (days 1-14) and the secretory phase (days [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. The exclusion criteria of this study included patients who received hormonal treatment or any anti-inflammatory treatment for ≥6 months prior to surgery.…”

Interaction with angiotensin-converting enzyme-encoding gene in female infertility: Insertion and deletion polymorphism studies

“…The pregnancy complications have been found to be related to thrombophilic polymorphisms (examples: MTHFR, FVL, ACE and PII), explains about ∼30% of obstetrical problems including pregnancy complications such as RPL (Goodman et al, 2009). Previous studies have examined the role of the angiotensin-converting enzyme-1 (ACE1) gene in male and female infertility factors including PCOS and endometriosis (Li et al, 2016, Kowalczyńska et al, 2014, Kucera et al, 2001, Kowalczyńska et al, 2011, Khan et al, 2014). PCOS is the leading cause of ovulatory infertility, affecting 5–7% of women of reproductive age, and the renin–angiotensin system (RAS) activity in PCOS suggests an important correlation between the RAS and PCOS.…”