Increased risk of polycystic ovary syndrome (PCOS) associated with CC genotype of miR-146a gene variation

Abstract

Polycystic ovary syndrome (PCOS) is an endocrinopathy in reproductive-age women believed to be affected by several genetics and environmental factors or both. Different miRNAs are one of such genetic factors that their associations with PCOS have been implicated. For instance, miR-146a that is well known for strongly regulating the immune response and inflammation was upregulated in serum plasma, follicular fluid and granulosa cells of PCOS patients. Different studies have shown that genetic changes in pre-miRNA can cause change in the expression or biological function of mature miRNA. Therefore, the main aim of this study was to investigate the association of miR-146a gene variation (rs2910164) with the susceptibility to PCOS. This study consists of 180 patients with PCOS and 192 healthy women matched by age and geographical region. Genotyping were determined by using PCR-RFLP in all subjects. The genotype frequency and allele distributions of all subjects were evaluated using Fisher’s exact test directed by SPSS v.20. The genotype and allele frequencies of the miR-146a polymorphism (rs2910164) significantly differ between PCOS and healthy controls. The frequencies of CC genotype (p = .054) and ‘C’ allele (p = .0001) of the miR-146a variant indicated a significant incidence in cases compared to controls. Such association was obtained in co-dominant (OR = 3.16) and dominant (OR = 2.29) models. Result of this study can be proposed that women with miR-146a variation are at a higher risk for developing PCOS, which can be due to up-regulation of miR-146a.

Chinese abstract

多囊卵巢综合征（PCOS）是育龄妇女内分泌疾病, 受多种遗传和环境因素的影响, 或两者兼有。不同的miRNA是与PCOS相关的遗传因素之一。例如, 众所周知的强调节免疫应答和炎症的miR-146a在PCOS患者的血清血浆、卵泡液和颗粒细胞中被上调。不同的研究表明, 前miRNA的遗传改变可导致成熟miRNA的表达或生物学功能的改变。因此, 本研究的主要目的是研究miR-146a基因变异（rs2910164）与PCOS易感性的关系。本研究包括180例PCOS患者和192例年龄和地理区域相匹配的健康女性。应用PCR-RFLP法检测所有受试者的基因分型。用SPSS v.20指导的Fisher精确检验评价所有受试者的基因型频率和等位基因分布。 miR-146a多态性（rs2910164）的基因型和等位基因频率在PCOS和健康对照组之间有显著性差异。miR-146a变异的CC基因型频率（p＝.054）和“C”等位基因频率（P＝.0001）与对照组相比有显著的发生率。在共显性（OR＝3.16）和显性（OR＝2.29）模型中得到了这种关联。这项研究的结果可以提出, miR-146a变异的女性发生PCOS的风险更高, 这可能是因miR-146a的上调所致。

Keywords:

• PCOS
• miR-146a
• gene polymorphism
• Iranian women

Disclosure statement

We certify that there is no conflict of interest with any financial organization.

Additional information

Funding

This article has been obtained from a grant number: 95GRN1M32855. We thanks all cooperating with us in conduction of this project, particularly the respectful populates and officials of Shahrekord University and Shahrekord University of Medical Sciences.