Association Study of Non-Coding RNA miR-499 and miR196a2 Gene Polymorphisms with the Risk of Idiopathic Recurrent Pregnancy Loss

Abstract

Background: MicroRNAs (miRNAs) play significant roles in several physiological procedures such as embryo implantation. Recently, findings have indicated that aberrant miRNAs gene expression and single nucleotide polymorphism in the gene encoded miRNAs may be contributed to the pathogenesis of recurrent pregnancy loss (RPL). This investigation aimed to examine potential associations between the two precursor miRNA SNPs miR-196a2 T > C and miR-499 A > G and susceptibility to RPL. Methods: We were analyzing a total of 200 subjects, which consisted of 100 women who experienced three or more recurrent miscarriages and 100 healthy women with one child and without historical aberrations. The genotypic frequencies of two SNPs were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to assess the association between the presence miRNA gene variant with the risk of RPL. Results: The genotypes frequency of miR-499 gene polymorphism AA/AG + GG and GG/AG + AA showed a statistically significant association with the risk of RPL (P = 0.019; OR = 2.003; 95% CI, 1.116 -3.594) and (P = 0.024; OR = 2.100; 95% CI, 1.095 -4.025), respectively. The genotypes frequency of miR-196a2 gene polymorphisms did not reveal a statistically significant difference across the two groups (P > 0.05). Conclusions: Our findings proposed that nucleotide changes in miR-499 gene encoding region may be contributed as a genetic predisposition factor to RPL, whereas the miR-196a2 gene variation cannot be a negative effect on pregnancy outcome.

Association of microRNA gene polymorphisms with recurrent spontaneous abortion: An updated meta‑analysis

“…However, the results of the present study showed no significant association. These results were consistent with the study by Alipour et al ( 14 ), Babakhanzadeh et al ( 16 ) and Fazli et al ( 17 ). The results of the present study contradicted the findings of the meta-analysis conducted by Srivastava et al ( 31 ), which suggested that miR-196a2 T>C polymorphism may be responsible for recurrent spontaneous abortion.…”

“…It is hypothesized that miR-499 expression deregulation and dysfunctions caused by gene mutations can affect female reproduction and fertility. Studies conducted by Alipour et al ( 14 ), Fazli et al ( 17 ) and Parveen et al ( 23 ) found a significant association of miR-499a with patients with RSA, which is consistent with the conclusion of the present study. Other trials yielded inconsistent results with no significant correlation with RSA ( 15 , 19 ).…”

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

“…The association of microRNA polymorphisms with recurrent spontaneous abortion (RSA) was frequently reported in different studies and showed a significant correlation of miR-146aC>G, miR-196a2T>C, and miR-499A>G with idiopathic recurrent spontaneous abortion [19][20][21]. In contrast, Fazil et al failed to show any relationship between the increased rates of recurrent miscarriage and miR-196a2 gene variation; however, they considered miR-499 gene variant to be a predisposing factor [22]. A recent study that investigated the link between polymorphisms in miRNA-196a2 and miRNA-499 in maternal blood and the placentas of patients with preeclampsia reported miRNA-196a2 rs11614913 variant to be a protective factor for preeclampsia predisposition among the studied group [23].…”

Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study

“…Of those, SNPs that resided in genes encoding microRNAs (miRNAs or miRs) have been brought to the attention [ 10 ]. Essentially, a significant proportion of IRSM might be due to SNPs in coding- or noncoding genome [ 11 ].…”