Significance of the lncRNAs MALAT1 and ANRIL in occurrence and development of glaucoma

Abstract

Background: Primary open-angle glaucoma (POAG) is the commonest form of glaucoma which is estimated to cause bilaterally blind within 11.1 million people by 2020.Therefore, the primary objectives of this study were to investigate the clinical significance of single-nucleotide polymorphisms (SNPs) in the lncRNAs MALAT1 and ANRIL in a Chinese Han POAG cohort.Methods: Three hundred and forty-six glaucoma patients and 263 healthy controls were recruited, and totally 14 SNPs in MALAT1 and ANRIL were genotyped between the two populations. Results:The MALAT1 SNPs rs619586 (A>G), rs3200401 (C>T), and rs664589 (C>G) were associated with POAG risk, and the ANRIL SNPs rs2383207 (A>G), rs564398 (A>G), rs2157719 (A>G), rs7865618 (G>A), and rs4977574 (A>G) were associated with POAG (p < 0.05). The MALAT1 haplotypes ACG and ATC, comprised rs619586, rs3200401, and rs664589, increased POAG risk, and the ANRIL haplotype AAGAA, made up of rs2383207, rs7865618, rs4977574, rs564398, and rs2157719, show a significantly increased risk of POAG. In addition, rs619586 (A>G) of MALAT1 and rs564398/rs2157719 of ANRIL were associated with a smaller vertical cup-to-disc ratio, while rs619586 of MALAT1 and rs2383207/rs4977574 of ANRIL were associated with higher intraocular pressure in the POAG population. Conclusion: Single-nucleotide polymorphisms and haplotypes in ANRIL and MALAT1were associated with POAG onset in our study population, which provide more possibilities to POAG diagnosis and treatment.

Potential roles of lncRNA MALAT1-miRNA interactions in ocular diseases

“…In a study of 346 glaucoma patients (diagnosed based on structural and functional changes in the optic disc and visual field measurements or an open angle by gonioscopy) and 263 healthy controls, MALAT1 SNPs rs619586 (A > G), rs3200401 (C > T), and rs664589 (C > G) were associated with primary open‐angle glaucoma (POAG) risk. The MALAT1 haplotypes ACG and ATC, comprised of rs619586, rs3200401, and rs664589, increased POAG risk (Huang et al 2022). It is also hypothesized that protein‐coding genes containing significant SNPs may possess response elements that affect the expression of MALAT1 (Yang et al 2014)], which has been implicated in many diseases, including glaucoma (Lv et al 2019; Chen et al 2017).…”

The Long Non-Coding RNA ANRIL in Cancers

“…Initially, the CDKN2A / ARF gene was found to be frequently inactivated or mutated in melanoma and other cancers, at least in part due to its ability to modulate the p53 axis [ 30 ]. Further investigations allowed researchers to link the 9p21 locus to various other abnormal situations, including atherosclerosis, T2D, Alzheimer’s disease, lupus erythematosus, epilepsy, glaucoma, obsessive compulsive disorder and sepsis [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The specific genetic variants and mechanisms underlying these associations are complex and continue to be the subject of ongoing research.…”

Diabetic Retinopathy: Are lncRNAs New Molecular Players and Targets?

“…The Antisense Non coding RNA in the INK4 Locus ( ANRIL ), also known as CDKN2B Antisense RNA 1 ( CDKN2B-AS1 ) is located in the 9p21.3 genomic region, within CDKN2B - CDKN2A gene cluster that has been reported as a susceptibility locus for cardiovascular disease [ 73 , 74 ], cancer [ 75 ], intracranial aneurysm [ 76 ], periodontitis [ 77 ], Alzheimer’s disease [ 78 ], endometriosis [ 79 ], glaucoma [ 80 ] and type 2 diabetes [ 81 ]. The upregulation of ANRIL has been reported in patients with DR compared to healthy subjects [ 62 ].…”