Biomarker potential of hsa-miR-145-5p in peripheral whole blood of manic bipolar I patients

Objective: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. Methods: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. Results: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. Conclusion: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

Biomarker potential of hsa-miR-145-5p in peripheral whole blood of manic bipolar I patients.

OBJECTIVE: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. METHODS: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. RESULTS: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. CONCLUSION: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

Genetic Predisposition to Unexplained Recurrent Pregnancy Loss: Killer Cell Immunoglobulin-Like Receptor Gene Polymorphisms as Potential Biomarkers.

AIM: The aim of this study was to investigate the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and unexplained recurrent pregnancy loss (URPL). MATERIALS AND METHODS: This study included 70 URPL patients with a history of two or more miscarriages and 70 healthy multiparous women as a control group. KIR genotyping was performed in all subjects for the KIRs 2DL1-4 and 2DS1-5 genes using polymerase chain reaction with sequence-specific primers. RESULTS: There was a significant relationship between the KIR genotypes and URPL. We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype was not detected in either the case or control group. Gene-gene interactions for all genes were statistically significant. The KIR Bx genotype was found primarily in the case group, and at a higher frequency when compared with the control group. There was a significant relationship between the URPL cases and Bx haplotypes. CONCLUSION: We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype of the KIR gene, however, was not detected in either the case or control group. The observations reported herein on KIR genotyping offer a new avenue for innovations in biomarker research concerning URPL and other complex obstetrics diseases.

Folate metabolism gene polymorphisms and risk for down syndrome offspring in Turkish women.

AIMS: Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Six common polymorphisms in folate-metabolizing genes were analayzed to determine possible risk factors for a child to be born having DS (DS mothers); these samples were taken from 47 Turkish mothers having DS children (case group) and 49 control mothers. Investigated polymorphisms include methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), A1298C (rs1801131), methionine synthase reductase (MTRR) A66G (rs1801394), methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A (rs2236225), reduced folate carrier (RFC1) A80G (rs1051266), and cystathionine ß-synthase (CBS) 844ins68. RESULTS: The frequency of the MTHFR 677C allele in DS mothers (79.8%) was significantly higher than in controls (66.3%), with a 0.499-fold increased risk of having a DS offspring (p=0.038 and 95% confidence interval [CI], 0.259-0.961). Mothers with the MTHFD1 1958A allele had a 1.880-fold increased risk of having a child with DS (p=0.031 and 95% CI, 1.060-3.335). No significant association was found for the other polymorphic variants in this study. Gene-gene interactions were not statistically significant. CONCLUSION: Polymorphic variants of the enzymes involved in folate metabolism may play an important role in determining the susceptibility of having a DS offspring. The gene-nutrition, gene-gene interactions and ethnicity are important variables to be considered in future studies.