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Long noncoding RNA HOTAIR polymorphisms and susceptibility to bipolar disorder: a preliminary case-control study
Saman Sargazi1, Armin Zahedi Abghari1,2, Shekoufeh Mirinejad1
1Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
Nucleosides, Nucleotides & Nucleic Acids
|April 26, 2022
Summary
Genetic variations in the HOX Transcript Antisense Intergenic RNA (HOTAIR) gene are linked to bipolar disorder (BD) risk and subtypes. Specific HOTAIR polymorphisms influence the likelihood of developing BD type II, with some increasing risk and others offering protection.
Area of Science:
- Genetics
- Psychiatry
- Molecular Biology
Background:
- Long noncoding RNAs (lncRNAs) are implicated in the pathogenesis of bipolar disorder (BD).
- The HOX Transcript Antisense Intergenic RNA (HOTAIR) gene is a key lncRNA with potential roles in various diseases.
Purpose of the Study:
- To investigate the association between four HOTAIR gene polymorphisms and the risk of bipolar disorder (BD).
- To explore the influence of these polymorphisms on clinical subtypes of BD, specifically BD type II (BDII).
Main Methods:
- Genotyping of four HOTAIR polymorphisms (rs1899663, rs12826786, rs4759314, rs920778) in 194 BD patients and 163 healthy controls.
- Utilized Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Amplification Refractory Mutation System-PCR (ARMS-PCR) for genotyping.
- Analyzed genetic associations under various models (allelic, recessive, dominant, codominant) and evaluated haplotype effects.
Main Results:
- Significant associations were found between HOTAIR polymorphisms (rs1899663, rs12826786, rs4759314, rs920778) and BD risk.
- Specific genotypes (rs920778 CT, rs1899663 GT, rs12826786 CT) increased BD type II risk.
- The rs4759314 GG genotype significantly reduced BDII risk by 83%.
- CTTA and CTCG haplotypes showed a positive association with BD risk.
Conclusions:
- HOTAIR gene polymorphisms interact to influence the development of bipolar disorder and its subtypes.
- These findings highlight the potential role of HOTAIR variations in BD pathogenesis.
- Further functional studies are required to understand the impact of these genetic variations on HOTAIR expression and epigenetic regulation.
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