Association between functional polymorphisms in the promoter of the miR-143/145 cluster and risk of intracranial aneurysm

Abstract

MicroRNAs (miRs)-143/145 are involved in various biological processes related to aneurysm formation and are downregulated in patients with intracranial aneurysm (IA). We aimed to determine whether two functional polymorphisms (i.e. rs4705342 and rs4705343) in the promoter of miR-143/145 are related to IA risk. A case-control study was undertaken to examine the association of rs4705342 and rs4705343 with IA risk, including 565 patients with IA and 622 age- and gender-matched controls. rs4705342 was analysed by TaqMan Assay, and rs4705343 was genotyped using polymerase chain reaction-restriction fragment length polymorphism. miR-143/145 expression was quantified using RT-PCR. rs4705342 was associated with a significantly lower risk of IA, with adjusted ORs of 0.74 (95% CI: 0.58–0.95) for TC genotype carriers and 0.74 (95% CI: 0.59–0.94) for TC/CC genotypes carriers. Individuals carrying the rs4705342 C allele had a reduced risk of IA (adjusted OR = 0.82; 95% CI: 0.68–0.98). Haplotype of the two loci of rs4705342 and rs4705343 showed that the CT haplotype carried a lower IA risk and higher miR-143 level. Moreover, the rs4705342 CC/CT genotypes were associated with higher miR-143 levels. Thus, the rs4705342C-rs4705343T haplotype in the promoter of miR-143/145 cluster may be related to IA development.

RETRACTED ARTICLE: Long Non-coding RNA MALAT1/microRNA-143/VEGFA Signal Axis Modulates Vascular Endothelial Injury-Induced Intracranial Aneurysm

“…Moreover, a clinical study has presented that the miR-143/145 cluster of IA patients is downregulated compared to healthy subjects [11]. In addition, it is previously discussed that miR-143/145 takes part in various biological processes associated with aneurysm formation and is downregulated in patients with IA [20]. All these findings are more or less echoed with the previous exploration outcomes.…”

“…A previous study has demonstrated the involvements of lncRNA-related competitive endogenous RNA networks in IA [19]. Also, a recent study has provided a proof that functional polymorphism in miR-143/145 gene promoter region is connected with the risk of IA [20]. In a study conducted by Xu et al, it is shown that overexpression of angiogenic factors, such as VEGFA, may be related to IA formation and rupture [21].…”

Analysis of association of potentially functional genetic variants within genes encoding miR-34b/c, miR-378 and miR-143/145 with prostate cancer in Serbian population

“…Since miR-143 and miR-145 are among the most commonly downregulated miRNAs in neoplasms such as gastric, urinary bladder, colorectal cancer, as well as PCa, genetic variants potentially affecting the expression of their precursor have been investigated in multiple malignant diseases. Among a number of SNPs located within the potential regulatory region of miR-143/145 cluster, the effect on transcriptional actions was revealed for rs4705343 and rs4705342 (Wei et al, 2016[ 35 ], Sima et al, 2017[ 32 ]). Also, a previous report suggests the association of genetic variant rs4705342 with PCa (Chu et al, 2016[ 7 ]).…”

Association between ELP4 rs986527 polymorphism and the occurrence and development of intracranial arachnoid cyst

“…Local mass effects may contribute to local neurological deficits depending on adjacent neural structures or bone anatomy. These lesions may also rupture, leading to subdural hematomas or hemorrhage (Sima, Sun, & Zhou, ). In this paper, we investigated the association between elongator protein complex 4 ( ELP4 ) rs986527 polymorphism and the occurrence and development of intracranial arachnoid cysts.…”