Association of ACE I/D and AGTR1 A1166C Gene Polymorphisms and Risk of Uterine Leiomyoma: A Case-Control Study.

Farshid Keshavarzi,Mojgan Mokhtari,Farahnaz Farzaneh,Darya Najafi,Saeedeh Salimi,Batool Teimoori

doi:10.31557/apjcp.2019.20.9.2595

Abstract

Objective:Uterine leiomyoma (UL) can be considered as the most common benign gynecological tumors of the smooth muscle cells in the myometrium. They are likely to be associated with infertility and recurrent abortion as well as obstructed labor and post-partum hemorrhage. Moreover, altered vascular-related genes can be linked to developing leiomyoma. Polymorphisms of the angiotensin-converting enzyme (ACE) gene are associated with some vascular diseases. The present study was carried out to investigate the association of ACE I/D and AGTR1 A1166C gene polymorphisms and the risk of uterine leiomyoma in a sample of Iranian population. Methods:The study was carried out on a total of 413 women divided into 202 patients with diagnosed uterine leiomyomas and a control group of 211. Genotyping was performed using the PCR or PCR-RFLP methods. Results:The ID and DD genotypes of ACE I/D polymorphism were associated with 2 and 2.9 fold higher risk of UL compared to II genotype (OR, 2 [95% CI, 1.3 to 3.2]; P = 0.004 and OR, 2.9 [95% CI, 1.6 to 5]; P = 0.0002). The frequencies of ACE D alleles were 53.7% in women with UL and 40.3% in controls, which were observed to be statistically different (P < 0.0001). The alleles and genotypes of AGTR1 A1166C polymorphism were not different between UL and control women (P=0.9). Conclusion:The ACE ID and DD genotypes were associated with a higher risk of UL. No relationship was found between AGTR1 A1166C polymorphism and UL.

Highlights

Uterine leiomyomas (ULs) can be considered as the most common benign monoclonal tumors of the smooth muscle cells in the myometrium (Flynn et al, 2006)
The present study was carried out to investigate the association of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism (I/D) and angiotensin receptor type 1 (AGTR1) A1166C gene polymorphisms and the risk of uterine leiomyoma in a sample of Iranian population
The ID and DD genotypes of ACE I/D polymorphism were associated with 2 and 2.9 fold higher risk of UL compared to II genotype (OR, 2 [95% CI, 1.3 to 3.2]; P = 0.004 and OR, 2.9 [95% CI, 1.6 to 5]; P = 0.0002)

Summary

Introduction

Uterine leiomyomas (ULs) can be considered as the most common benign monoclonal tumors of the smooth muscle cells in the myometrium (Flynn et al, 2006). Evidence suggests that 70% of women may develop uterine fibroids This disorder may be without signs and symptoms, in 40 to 50 percent of women over age 35 it may present as menorrhagia, infertility, pain, and recurrent pregnancy loss (RPL) (Marino et al, 2004; Wang et al, 2015). Several mechanisms have been suggested that have the effects on growth of UL, including ovarian angiogenesis, steroid hormones, growth factors, and apoptosis related factors (Wang et al, 2002). Both abnormal angiogenesis and vascular-related growth factors have been considered to be associated with the UL pathogenesis and growth. It is believed that ACE activity may be related to tumor growth and ACE inhibitors as well as angiotensin receptor blockers, thereby contributing to the suppression of tumor growth

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Conclusion