Association of Polymorphisms within HOX Transcript Antisense RNA (HOTAIR) with Type 2 Diabetes Mellitus and Laboratory Characteristics: A Preliminary Case-Control Study

Abstract

Type 2 diabetes mellitus (T2DM) is a complex heterogeneous disease resulting from the environment and genetic interactions. Lately, genetic association studies have shown that polymorphisms in long noncoding RNAs (lncRNAs) are associated with T2DM susceptibility. This preliminary study is aimed at investigating if HOX transcript antisense RNA (HOTAIR) polymorphisms contribute to T2DM development. Five hundred clinically diagnosed T2DM cases and 500 healthy controls were recruited from the southeast Iranian population. Genomic DNA was isolated from nucleated blood cells and genotyped for MspI (C/T) (rs920778) and AluI (A/G) (rs4759314) polymorphisms using the PCR-RFLP technique. For genotyping rs12826786 C/T and rs1899663 G/T variants, ARMS-PCR method was applied. Our findings indicated that HOTAIR rs920778 C/T, rs12826786 C/T, and rs4759314 A/G polymorphisms have a significant positive association with T2DM, while a negative association was observed between rs1899663 G/T T2DM susceptibility. Significant associations were also observed between rs920778 C/T and HDL-C as well as s4759314 A/G and both FBS and LDL-C in T2DM patients. Haplotype analysis indicated that the CGCG, CTTG, TGTA, and TTTG haplotypes of rs920778/rs1899663/rs12826786/rs4759314 significantly enhanced T2DM risk by 1.47, 1.96, 2.81, and 4.80 folds, respectively. No strong linkage disequilibrium was found between the four HOTAIR SNPs. We firstly reported that HOTAIR rs1899663 G/T, rs12826786 C/T, rs4759314 A/G, and rs920778 C/T polymorphisms might influence T2DM susceptibility by modulating different signaling pathways and could be regarded as potential prognostic markers in T2DM patients.

Association of CYP7A1 and CYP2E1 Polymorphisms with Type 2 Diabetes in the Chinese Han Populations

“… 33 HOTAIR rs920778 C/T, rs12826786 C/T, rs4759314 A/G polymorphisms were positively correlated with T2DM, while rs1899663 G/T was negatively correlated with T2DM susceptibility. 34 In our study, the levels of TC and LDL were significantly different in rs8192879TT, TC and CC genotypes in T2DM patients. Genome-wide association studies revealed that CYP7A1 rs2081687 is an SNP associated with lipids in African Americans.…”

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

“…Still, other mechanisms are involved in the pathogenesis of IRSM that remains to be fully elucidated. Such DNA variations might serve as a valuable prognostic factor to predict the risk of developing such gestational diseases and can be exploited in “Personalized Medicine” applications [ 67 , 68 ].…”

Immune-Related LncRNAs as Prognostic Factors for Pediatric Rhabdoid Tumor of the Kidney

“…LncRNAs account for about 80% of the human transcriptome, which interact with DNA, RNA, and protein to exert a powerful regulatory function, such as epigenetic modification, transcription control, and posttranscriptional modification [ 11 – 13 ]. LncRNAs are involved in essential biological processes within cells, including cell growth, cell differentiation, cell invasion, and cell cycle control [ 12 , 14 , 15 ]. Dysregulation of lncRNA is associated with several diseases [ 12 , 13 ].…”

“…LncRNAs are involved in essential biological processes within cells, including cell growth, cell differentiation, cell invasion, and cell cycle control [ 12 , 14 , 15 ]. Dysregulation of lncRNA is associated with several diseases [ 12 , 13 ]. Studies suggest that lncRNAs are deregulated in various cancers and played an important role in occurrence, development, and metastasis [ 14 , 16 – 20 ].…”

“…The potential mechanisms of action of lncRNAs in malignancies include chromatin remodeling induction, transcription interference, alternative splicing, production of endo-siRNAs or miRNAs called “miRNA sponges,” and altering the localization or activity of proteins [ 13 ]. Based on these mechanisms, the level and function of proteins and their related-signaling pathways, such as phosphatidylinositol 3-kinase (PI3K/Akt) pathway, NF-KB pathway, and tumor necrosis factor (TNF) pathway, may be dysregulated and thus result in the initiation, progression, and abnormal immune infiltration of cancer [ 12 – 15 ]. LncRNAs have been shown to be promising diagnostic biomarkers and therapeutic targets in different cancers [ 21 , 22 ].…”