ANRILas a genetic marker for cardiovascular events in renal transplant patients - an observational follow-up cohort study

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplant recipients. Several single-nucleotide polymorphisms (SNPs) in the ANRIL gene pathway have been associated with cardiovascular events (CE). The main objective was to ascertain whether ANRIL (rs10757278) and CARD8 (rs2043211) SNPs could mediate susceptibility to CE. This was an observational follow-up cohort study of renal transplant recipients at Bellvitge University Hospital (Barcelona) from 2000 to 2014. A total of 505 recipients were followed up until achievement of a CE. Patients who did not achieve the endpoint were followed up until graft loss, lost to follow-up or death. Survival analysis was used to ascertain association between genetic markers, clinical data, and outcome. Fifty-three patients suffered a CE after renal transplantation. Results showed a significant association between ANRIL SNP and CE. Homozygous GG for the risk allele showed higher risk for CE than A carriers for the protective allele [HR = 2.93(1.69-5.11), P < 0.0001]. This effect was maintained when it was analyzed in combination with CARD8, suggesting that CARD8 SNP could play a role in the ANRIL mechanism. However, our study does not clarify the molecular mechanism for the CARD8 SNP regulation by ANRIL. ANRIL SNP may predispose to the development of CE after successful kidney transplantation.

LncRNA ANRIL protects against oxygen and glucose deprivation (OGD)-induced injury in PC-12 cells: potential role in ischaemic stroke

“…Although the expression and functions of lncRNAs in stroke and neuroprotection remain not to be clarified [11], increasing evidence have prove that lncRNAs are closely involved in IS, such as maternally expressed gene 3 (MEG3), H19, CaMK2D-associated transcript 1 (C2dat1), Fos downstream transcript (FosDT), small nucleolar RNA host gene 14 (SNHG14), and taurine-upregulated gene 1 (TUG1) which have been found to affect cell apoptosis, inflammation, cell death, and angiogenesis in IS [12]. For example, previous study reported that lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) has been related with a higher risk of developing cardiovascular events and ANRIL was demonstrated to be associated with IS [13]. Meanwhile, ANRIL was reported to play a role in inflammatory responses and atherosclerosis [13,14].…”

“…For example, previous study reported that lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) has been related with a higher risk of developing cardiovascular events and ANRIL was demonstrated to be associated with IS [13]. Meanwhile, ANRIL was reported to play a role in inflammatory responses and atherosclerosis [13,14]. Moreover, one former study demonstrated that lncRNA ANRIL altered the expressions of vascular endothelial growth factor (VEGF) and apromoted ngiogenesis in rats [15], which provided potential effects of ANRIL in IS.…”

Mechanisms of Antisense Transcription Initiation with Implications in Gene Expression, Genomic Integrity and Disease Pathogenesis

“…In addition to the involvement of antisense RNAs in cardiac diseases via diabetes, antisense transcription/transcripts are also directly associated with cardiovascular diseases. Recent studies have implicated antisense RNAs as new diagnostic markers with therapeutic potentials for cardiovascular diseases [210,211,212,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236,237,238,239]. For example, an antisense transcript H19, discussed above, is associated with cardiovascular diseases such as CAD.…”

Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients

“…been investigated with large-scale GWAS approaches, although a handful of recent candidate gene studies have been published. [19][20][21][22] Given that etiologic factors explaining CV disease in RTRs might differ somewhat from those in the general population, one cannot automatically assume that the composite GRS investigated by Mega et al is valid for the transplant population. We therefore aimed to evaluate the predictive value of the risk score in RTRs by genotyping patients from the Assessment of Lescol in Renal Transplantation (ALERT) trial, 23,24 a study of mostly Caucasian, stable, and well-characterized RTRs followed for 7-8 years for validated clinical endpoints, including major cardiovascular events (MACEs).…”

“…[19][20][21][22] Given that etiologic factors explaining CV disease in RTRs might differ somewhat from those in the general population, one cannot automatically assume that the composite GRS investigated by Mega et al is valid for the transplant population. [19][20][21][22] Given that etiologic factors explaining CV disease in RTRs might differ somewhat from those in the general population, one cannot automatically assume that the composite GRS investigated by Mega et al is valid for the transplant population.…”