Combination effect of cytochrome P450 1A1 gene polymorphisms on uterine leiomyoma: A case-control study.

Saeedeh Salimi,Mojgan Mokhtari,Maryam Khodamian,Minoo Yaghmaie,Soodabeh Rezaee,Atefeh Yazdi,Abbas Mohammadpour-Gharehbagh,Mojtaba Sajadian

doi:10.17305/bjbms.2016.1245

Abstract

Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus, and estrogen metabolizing enzymes affect its progression. This study aimed to evaluate the association between two single-nucleotide polymorphisms of cytochrome P450 1A1 (CYP1A1) gene and UL risk. The study consisted of 105 patients with UL and 112 healthy women as controls. Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene were analyzed by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods, respectively. The findings indicated no association between Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene and UL (p < 0.05). However, the combination effect of TT/AG genotypes of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms was associated with 4.3-fold higher risk of UL. In addition, haplotype analysis revealed that TG haplotype of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms could increase the UL risk nearly 4.9-fold. Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms of CYP1A1 gene were not associated with UL susceptibility; however, the combination of the TT/AG genotypes and TG haplotype could increase the UL risk.

Highlights

Uterine leiomyoma (UL) as a common benign neoplasm of the uterus involves almost 30‐40% of reproductive age women
The Ile462Val (A/G) polymorphism conformed to the Hardy–Weinberg equilibrium in the UL patients; this polymorphism did not conform to Hardy–Weinberg equilibrium in the control group
There was no correlation between Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms of cytochrome P450 1A1 (CYP1A1) gene and the UL susceptibility, the combination effect of the TT/AG genotypes of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms was associated with 4.3‐fold higher risk of UL (odds ratio [OR], 4.3 [95% confidence inter‐ val (CI), 1.1 to 16.1], P = 0.03) (Table 3)

Summary

Introduction

Uterine leiomyoma (UL) as a common benign neoplasm of the uterus involves almost 30‐40% of reproductive age women. There are large amounts of extracellular matrix components in this tumor, including collagen, fibronectin, and proteogly‐ cans [1]. Race, caffeine, number of pregnancies, endoge‐ nous hormone levels (estrogen and progesterone), enzymes, obesity, and genetic factors are associated with UL risk [1,2]. UL may result in a number of problems such as hemorrhage in the first trimester, placenta displacement, pre‐ mature labor, and miscarriage [3,4]. The exact cause of the disease is unknown, the effects of hormonal, genetic, and growth factors on UL progression have been established [5]. Submitted: 28 March 2016/Accepted: 04 May 2016

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