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Association of Long Noncoding RNA HOTAIR Polymorphism and the Clinical Manifestations of Diabetic Retinopathy.

ABSTRACT: The aim of the current study is to evaluate the possible correlation between the single-nucleotide polymorphisms (SNP) of HOX transcript antisense intergenic RNA (HOTAIR) and the clinical characteristics of diabetic retinopathy (DR). Four loci of HOTAIR SNPs, including rs920778 (T/C), rs12427129 (C/T), rs4759314 (A/G), and rs1899663 (G/T), were genotyped via the TaqMan allelic discrimination for 276 DR individuals and 452 non-DR patients. The distribution frequency of HOTAIR SNP rs12427129 CT [adjusted odds ratio (AOR): 1.571, 95% CI: 1.025-2.408, p = 0.038], HOTAIR SNP rs12427129 CT+TT (AOR: 1.611, 95% CI: 1.061-2.446, p = 0.025), and HOTAIR SNP rs1899663 TT (AOR: 2.443, 95% CI: 1.066-5.595, p = 0.035) were significantly higher in the DR group. Moreover, the proliferative diabetic retinopathy (PDR) subgroup revealed a significantly higher distribution of HOTAIR SNP rs12427129 CT+TT (AOR: 2.016, 95% CI: 1.096-3.710, p = 0.024) and HOTAIR SNP rs1899663 TT (AOR: 4.693, 95% CI: 1.765-12.479, p = 0.002), and the distribution frequencies of HOTAIR SNP rs12427129 CT (AOR: 3.722, 95% CI: 1.555-8.909, p = 0.003), HOTAIR SNP rs12427129 CT+TT (AOR: 4.070, 95% CI: 1.725-9.600, p = 0.001), and HOTAIR SNP rs1899663 TT (AOR: 11.131, 95% CI: 1.521-81.490, p = 0.018) were significantly higher in the female PDR subgroup. Regarding the clinical characters, the DR patients with HOTAIR SNP rs1899663 GT+TT revealed a significantly shorter duration of diabetes compared to the DR patients with HOTAIR SNP rs1899663 GG (10.54 ± 8.19 versus 12.79 ± 7.73, p = 0.024). In conclusion, HOTAIR SNP rs12427129 and rs1899663 are strongly correlated to the presence of DR, especially for a female with PDR.

SUBMITTER: Chuang CC

PROVIDER: S-EPMC9658836 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Association of Long Noncoding RNA HOTAIR Polymorphism and the Clinical Manifestations of Diabetic Retinopathy.

Chuang Chih-Chun CC Wang Kai K Yang Yi-Sun YS Kornelius Edy E Tang Chih-Hsin CH Lee Chia-Yi CY Chien Hsiang-Wen HW Yang Shun-Fa SF

International journal of environmental research and public health 20221107 21

The aim of the current study is to evaluate the possible correlation between the single-nucleotide polymorphisms (SNP) of HOX transcript antisense intergenic RNA (HOTAIR) and the clinical characteristics of diabetic retinopathy (DR). Four loci of HOTAIR SNPs, including rs920778 (T/C), rs12427129 (C/T), rs4759314 (A/G), and rs1899663 (G/T), were genotyped via the TaqMan allelic discrimination for 276 DR individuals and 452 non-DR patients. The distribution frequency of HOTAIR SNP rs12427129 CT [a ...[more]

PMID: 36361470

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Project description:PurposeDiabetic retinopathy (DR) remains a pressing issue worldwide. Abnormal angiogenesis is a distinct vascular lesion in DR, and research has established that vascular endothelial growth factor A (VEGF-A) is a primary mediator of such changes. However, limitations in current anti-VEGF therapies suggest that our understanding of molecular networks underlying ocular angiogenesis remains far from complete. Based on our long non-coding RNA (lncRNA) array analyses, HOX antisense intergenic RNA (HOTAIR) was identified as one of the top upregulated lncRNAs in high glucose-cultured human retinal endothelial cells (HRECs). Given the well-documented roles of HOTAIR in cancer, no studies have examined the epigenetic implications of HOTAIR in DR, and we investigated such relationships herein.MethodsWe used HRECs exposed to various glucose concentrations and epigenetic modulators to examine HOTAIR, angiogenic, and DR-related molecular markers. Oxidative stress, angiogenesis, and mitochondrial dysfunction were assessed. Retinal tissues of diabetic rodents and the vitreous humor and serum of patients with proliferative DR were also investigated.ResultsHyperglycemia significantly augmented HOTAIR expression in HRECs and promoted angiogenesis, oxidative damage, and mitochondrial aberrations. Similarly, vitreous humor and serum from proliferative DR patients and retinas from diabetic animals demonstrated increased HOTAIR expression compared to non-diabetic controls. HOTAIR knockdown protected against glucose-induced increases of angiogenic and diabetes-associated molecules in the retina. Mechanistically, we showed that HOTAIR exerts its capabilities by preventing oxidative stress and modulating epigenetic pathways involving histone methylation, histone acetylation, DNA methylation, and transcription factors.ConclusionsOur findings suggest that HOTAIR is a critical lncRNA in the pathogenesis of DR and may potentially be important for diagnostic and therapeutic targeting.

Dataset Information

Association of Long Noncoding RNA HOTAIR Polymorphism and the Clinical Manifestations of Diabetic Retinopathy.

Publications

Association of Long Noncoding RNA HOTAIR Polymorphism and the Clinical Manifestations of Diabetic Retinopathy.

Similar Datasets

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