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.

Genetic Variants miR-126, miR-146a, miR-196a2, and miR-499 in Polycystic Ovary Syndrome

“…Hosseini et al in a study investigating the association of miR-146a and miR-222 polymorphisms with susceptibility to PCOS demonstrated the significant correlation of both SNPs with an increased risk of PCOS [ 17 ]. Similar to our results, Ebrahimi and others found a significantly higher rate of miR-146a variant incidence in cases compared to controls and considered miR-146a variation to lead to increased PCOS among their studied group [ 18 ].…”

The Translational Role of miRNA in Polycystic Ovary Syndrome: From Bench to Bedside—A Systematic Literature Review

“…Of these, 975 were excluded after title/abstract screening (not relevant to the review inclusion criteria). We examined the full text of 52 publications to summarize the possible translational role of miRNA in PCOS [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , …”

Genetic polymorphisms associated with polycystic ovary syndrome among Iranian women

“…Studies among women with PCOS have observed the upregulation of miR‐146a in granulosa cells, follicular fluid, and serum 119 . Bioinformatic data suggest that the target genes of miR‐146a are involved in cell cycle, apoptosis, and endocrine signaling pathways (e.g., Jak‐STAT, Wnt, and MAPK), indicative of the association of miR‐146a with pathogenesis of PCOS 17 .…”

“…Bioinformatic data suggest that the target genes of miR‐146a are involved in cell cycle, apoptosis, and endocrine signaling pathways (e.g., Jak‐STAT, Wnt, and MAPK), indicative of the association of miR‐146a with pathogenesis of PCOS 17 . Iranian studies have reported that the miR‐146a rs2910164 polymorphism is associated with a higher risk of PCOS 119,120 …”