Genetic Analysis of BDNF, GNB3, MTHFR, ACE and APOE Variants in Major and Recurrent Depressive Disorders in Russia

Bondarenko, Elena; Шадрина, М. И.; Grishkina, MN; Дружкова, Т. А.; Akzhigitov, R. G.; Gulyaeva, N. V.; Guekht, Alla; Slominsky, P. A.

doi:10.7150/ijms.16642

Cited by 20 publications

(19 citation statements)

References 29 publications

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“…Although miR-124 has been widely studied in animal models of depression, few studies have investigated the relationship between the levels of miR-124 and Mdd in clinics. Recent studies have reported that miR-124-3p was upregulated in the BA46 area of the brain (44) and in peripheral blood mononuclear cells in patients with Mdd (45). miR-124 expression levels were also increased in the hippocampus of rat models of depression (46,47).…”

Section: Discussionmentioning

confidence: 96%

“…These results revealed that miR-124-3p may regulate the mTOR signaling pathway by reducing the expression of ddIT4, which stabilizes the complex formed by TSc1 and TSc2; this complex subsequently inhibits mTORc1-dependent protein synthesis and cell growth (50). Research has demonstrated that miR-124-3p was correlated with cell growth, proliferation and apoptosis, as well as the mTOR pathway (45). diagnostically, Mdd is associated with smaller regional brain volumes (53).…”

Section: Discussionmentioning

confidence: 99%

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Downregulation of microRNA‑124‑3p suppresses the mTOR signaling pathway by targeting DDIT4 in males with major depressive disorder

Wang¹,

Zhao²,

Yang³

et al. 2017

Int J Mol Med

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Recent investigations have suggested that microRNAs (miRNAs or miRs) are involved in several pathways that may contribute to the pathomechanism of major depressive disorder (MDD). Sex may not only act as a demographic factor in clinical practive, but may also play a vital role in the molecular heterogeneity of MDD. Although many molecular changes correlated with MDD are found in males, the molecular mechanisms of MDD remain poorly understood. The present study performed bioinformatics analysis to investigate the pathomechanism of MDD in males. The present study identified miR‑124‑3p as one of the most dysregulated miRNAs in MDD, with decreased expression in the post‑mortem BA44 brain area of male patients with MDD. In addition, miR‑124‑3p targets DNA damage‑inducible transcript 4 (DDIT4) and specificity protein 1 (SP1), a DDIT4 transcription factor, in the validated target module of the miRWalk 2.0 database. This is concurrent with an increase in the expression level of DDIT4, which is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway. It was also demonstrated that miR‑124‑3p expression was positively associated with mTOR signaling and this relationship was dependent on the tuberous sclerosis proteins 1/2 complex. Taken together, these results provided a novel insight on miR‑124‑3p involvement in the biological alterations of male patients with MDD and suggested that this miRNA may also serve as a male‑speciﬁc target for antidepressant treatment.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑124‑3p suppresses the mTOR signaling pathway by targeting DDIT4 in males with major depressive disorder

Wang¹,

Zhao²,

Yang³

et al. 2017

Int J Mol Med

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“…[9–12] A large number of epidemiological studies have investigated the relationship between the C677T polymorphism of MTHFR and many diseases, including breast cancer, colorectal cancer, ischemic stroke, depressive disorders, and hypertension. [13–17]…”

Section: Introductionmentioning

confidence: 99%

Analysis of genetic polymorphism of methylenetetrahydrofolate reductase in a large ethnic Hakka population in southern China

Zhao

Hou

et al. 2018

Medicine

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Methylenetetrahydrofolate reductase (MTHFR) catalyzes conversion of methylene tetrahydrofolate to methylte trahydrofolate. MTHFR C677T polymorphism has been regarded as a risk factor for various vascular diseases. Our study aimed to investigate the distribution frequencies of this polymorphism among Hakka population living in southern China. We retrospectively recruited 5102 unrelated Chinese Hakka subjects. MTHFR C677T polymorphism was tested using the polymerase chain reaction (PCR) and DNA sequencing. A total of 2358 males and 2744 females (aged from 10 years to 101 years) were included in this study. In total, 2835 (55.63%) subjects were homozygous for the C allele (CC), 1939 (38.00%) subjects were heterozygous (CT), and 325 (6.37%) subjects were homozygous for the T allele (TT). The allelic frequency of mutant T was 25.37% with 325 individual homozygous for this defective allele resulting in a frequency of about 6.37% for the TT genotype. According to the study results, the overall frequency of MTHFR C677T genotypes did not differ significantly among the gender and age groups. Our study showed the prevalence of MTHFR C677T polymorphism in a large ethnic Hakka population living in southern China. It would be important implications for the primary prevention of various vascular diseases.

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“…The SNP and VNTR genotyping was carried out using locus-speci c PCR as described previously [40][41][42][43][44][45].…”

Section: Dna Isolation and Genotypingmentioning

confidence: 99%

Association of the SLC6A4, SLC6A3, COMT and BDNF Gene Polymorphisms with Suicidal Behavior: A Case Control Study

Rafikova

Шадрина

Slominsky

et al. 2020

Preprint

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BackgroundSuicide causes about 1 million deaths per year. Familial transmission of suicide, as well as the involvement of serotonin and dopamine systems in suicidal behavior, was confirmed by previous studies. We investigated an effect of 11 polymorphisms of 9 genes related to dopamine and serotonin transmission (SLC6A4, HTR1A, HTR2A, HTR1B, SLC6A3, DRD4, DRD2, COMT, and BDNF) on the risk of suicide. MethodsThe study was performed on 100 psychiatric clinic patients with repeated suicide attempts. Genomic DNA was obtained from venous blood. Genotyping was performed using locus-specific PCR. Statistical analysis was carried out using a Pearson Chi-squared test, ORs, with the corresponding 95% CIs and one-way ANOVA.ResultsAssociation of the SLC6A3 40–45 bp VNTR and SLC6A4 rs25531 loci with suicidal behavior was tested for the first time. We have shown that a short allele of SLC6A3 40–45 bp VNTR locus might increase the risk of suicidal attempts (p = 0.009). Contrary to previous research, we have found that the Val-allele of COMT rs4680 is associated with suicide (p = 0.028). T-allele of BDNF rs6264 and A-allele of SLC6A4 rs25531 were associated with suicidal behavior with p = 0.029 and p = 0.047, respectively. ANOVA showed the lack of association between these loci and severity of depressive symptoms, but revealed a possible effect of SLC6A4 40 bp VNTR and HTR1B loci on anxiety symptoms. ConclusionsOur results suggest that allelic variants of SLC6A3, SLC6A4, COMT and BDNF genes might be considered as risk factors for repeated suicide attempts in patients with different mental disorders. Loci SLC6A4 40 bp VNTR and HTR1B rs6296 may affect anxiety symptoms.

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Genetic Analysis of BDNF, GNB3, MTHFR, ACE and APOE Variants in Major and Recurrent Depressive Disorders in Russia

Cited by 20 publications

References 29 publications

Downregulation of microRNA‑124‑3p suppresses the mTOR signaling pathway by targeting DDIT4 in males with major depressive disorder

Downregulation of microRNA‑124‑3p suppresses the mTOR signaling pathway by targeting DDIT4 in males with major depressive disorder

Analysis of genetic polymorphism of methylenetetrahydrofolate reductase in a large ethnic Hakka population in southern China

Association of the SLC6A4, SLC6A3, COMT and BDNF Gene Polymorphisms with Suicidal Behavior: A Case Control Study

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