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Association of MIR137 With Symptom Severity and Cognitive Functioning in Belarusian Schizophrenia Patients
Hanna Kandratsenka1, Anastasiya Nestsiarovich2, Inna Goloenko1
1Laboratory of Cytoplasmic Inheritance, Institute of Genetics and Cytology, National Academy of Sciences of the Republic of Belarus, Minsk, Belarus.
Abstract:
MicroRNA-137 (miRNA-137; miR-137) is one of the important post-transcriptional regulators of the nervous system development, and its MIR137 gene rs1625579 polymorphism was reported to be a potential regulator for schizophrenia susceptibility. However, schizophrenia characteristics controlled by MIR137 rs1625579 polymorphism are still insufficiently understood. There were 3 groups included in the study: (a) subjects with diagnosis of schizophrenia (n = 150; 81-females, 69-males), (b) mentally healthy people (control group; n = 102; 66-females, 36-males) and (c) Belarusian indigenous male group (n = 295). Associations of rs1625579 with schizophrenia, symptom's severity and cognitive performance [by using Positive and Negative Syndrome Scale (PANSS) and Wisconsin Card Sorting Test (WCST), respectively] were studied, when compared to controls. Allele and genotype frequencies were investigated in Belarusian indigenous males. Rs1625579 displayed no association with schizophrenia in Belarusian population. Significant "symptom severity-genotype" interactions were revealed for schizophrenia patients. Patients with T/G genotype displayed lower severity of positive symptoms and general psychopathology compared to homozygous subjects. T/T genotype was associated with the highest symptom's severity. The negative symptom scores and the total PANSS-score were significantly higher in females carrying genotype T/T vs. T/G+G/G; no significant gene-phenotype associations were found in males. WCST parameters did not show any association with rs1625579 polymorphism. MIR137 rs1625579 polymorphism might be an important sex-dependent factor influencing severity of schizophrenia psychopathological manifestations. These findings also contribute to the knowledge on candidate gene effects on characteristics related to schizophrenia phenotype. As miR 137 is considered to be cancer therapeutic target, miR-137 may also explain the lower incidence of cancer in schizophrenia patients. Further studies with larger sample size are needed to confirm these novel findings.
Insights
The MIR137 rs1625579 polymorphism influences schizophrenia symptom severity, particularly in females. This genetic variation did not associate with schizophrenia risk but impacted symptom presentation, suggesting a sex-dependent role in the disorder.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- MicroRNA-137 (miRNA-137) is crucial for nervous system development.
- The MIR137 gene rs1625579 polymorphism is a potential factor in schizophrenia susceptibility.
- Understanding the specific impact of this polymorphism on schizophrenia characteristics is limited.
Purpose of the Study:
- To investigate the association of MIR137 rs1625579 polymorphism with schizophrenia.
- To analyze the relationship between this polymorphism and schizophrenia symptom severity (positive, negative, general psychopathology).
- To assess the impact of the polymorphism on cognitive performance in schizophrenia patients.
Main Methods:
- Case-control study comparing schizophrenia patients (n=150) and healthy controls (n=102).
- Analysis of allele and genotype frequencies in a Belarusian population (including indigenous males, n=295).
- Assessment of symptom severity using the Positive and Negative Syndrome Scale (PANSS) and cognitive function with the Wisconsin Card Sorting Test (WCST).
Main Results:
- Rs1625579 showed no association with schizophrenia risk in the Belarusian population.
- Significant gene-genotype interactions were found for symptom severity in schizophrenia patients.
- The T/T genotype was linked to higher symptom severity, while T/G genotype correlated with lower positive symptoms and general psychopathology.
- Sex-dependent effects were observed: females with T/T genotype had higher negative symptom scores and total PANSS scores compared to T/G+G/G genotypes.
- No significant associations were found between rs1625579 and cognitive performance (WCST).
Conclusions:
- The MIR137 rs1625579 polymorphism may be a sex-dependent factor influencing schizophrenia symptom severity.
- Findings contribute to understanding candidate gene effects on schizophrenia phenotype.
- The potential role of miR-137 in cancer therapeutics and its link to lower cancer incidence in schizophrenia patients warrants further investigation.
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