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Genetic Polymorphisms in miR-137 and Its Target Genes, TCF4 and CACNA1C, Contribute to the Risk of Bipolar Disorder:
Mohammad Ali Mokhtari1, Saman Sargazi2, Ramin Saravani1,2
1Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan 98167-43463, Iran.
Disease Markers
|October 4, 2022
Summary
Genetic variations in miR-137, TCF4, and CACNA1C are associated with bipolar disorder (BD) susceptibility. These findings highlight potential genetic markers for BD risk. Further research is needed for confirmation across diverse populations.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- MicroRNA-137 (miR-137) and its target genes, CACNA1C and TCF4, are strongly implicated in psychiatric disorders.
- Genetic variations in these genes may influence susceptibility to bipolar disorder (BD).
Purpose of the Study:
- To investigate the association between specific genetic variations (SNPs) in miR-137, TCF4, and CACNA1C and their impact on BD susceptibility.
- To explore the functional consequences of these genetic variations using bioinformatics analyses.
Main Methods:
- Genotyping of 252 BD patients and 213 healthy controls using PCR-RFLP and ARMS-PCR.
- Analysis of single nucleotide polymorphisms (SNPs): miR-137 (rs1625579A/C), TCF4 (rs1261084C/T), CACNA1C (rs10774053A/G and rs10466907G/T).
- Bioinformatics analyses to predict the functional impact of SNPs on gene regulation.
Main Results:
- Significant associations were found between TCF4 rs1261084C/T, CACNA1C rs10466907G/T, and CACNA1C rs10774053A/G polymorphisms and increased BD risk under various genetic models.
- Specific genotype combinations (e.g., TT/AG/GT/AA, TT/GG/GT/AC) were strongly linked to elevated BD risk.
- Bioinformatics revealed that SNPs can alter miRNA binding sites in TCF4 and CACNA1C, and affect splicing factor binding for CACNA1C.
Conclusions:
- All studied single nucleotide polymorphisms (SNPs) in miR-137, TCF4, and CACNA1C show a positive association with BD susceptibility.
- These genetic variations may play a role in the molecular mechanisms underlying BD.
- Replication studies in diverse ethnic groups are necessary to validate these preliminary findings.
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