Influence of Polymorphic Gene Variants of the Dopaminergic System on the Risk of Disorders with Depressive Symptoms
Depression is characterized by extremely high clinical heterogeneity. Only a few of the many symptoms of depression may overlap in different people with major depressive disorder. The search for molecular genetic markers of depression often yields conflicting results, which may be due to the heterog...
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| Veröffentlicht in: | Russian journal of genetics Jg. 57; H. 8; S. 942 - 948 |
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01.08.2021
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| ISSN: | 1022-7954, 1608-3369 |
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| Abstract | Depression is characterized by extremely high clinical heterogeneity. Only a few of the many symptoms of depression may overlap in different people with major depressive disorder. The search for molecular genetic markers of depression often yields conflicting results, which may be due to the heterogeneity of the samples. The aim of this work was to identify genetic risk factors for three diseases characterized by severe depressive symptoms. All participants were of East Slavic origin from Moscow and the regions of Central Russia. The polymorphisms of the genes of the dopamine transporter (
SLC6A3/DAT1
), dopamine receptors (
DRD4
and
DRD2
), and the enzyme catechol-
O
-methyltransferase (
COMT
) were studied in patients with three diagnoses: depressive episode, recurrent depression, and mixed anxiety and depressive disorder. We observed statistically significant differences in the distribution of alleles for the
SLC6A3
(
DAT1
) 40 bp VNTR locus in patients with mixed anxiety and depressive disorder. The short allele (
8R
and
9R
) was more common in patients than in the control group (
p
= 0.005); significant differences were also observed in the distribution of genotypes of this locus (
p
= 0.025). No associations were found between the loci of the dopaminergic system and the risk of depressive episode and recurrent depression. |
|---|---|
| AbstractList | Depression is characterized by extremely high clinical heterogeneity. Only a few of the many symptoms of depression may overlap in different people with major depressive disorder. The search for molecular genetic markers of depression often yields conflicting results, which may be due to the heterogeneity of the samples. The aim of this work was to identify genetic risk factors for three diseases characterized by severe depressive symptoms. All participants were of East Slavic origin from Moscow and the regions of Central Russia. The polymorphisms of the genes of the dopamine transporter (
SLC6A3/DAT1
), dopamine receptors (
DRD4
and
DRD2
), and the enzyme catechol-
O
-methyltransferase (
COMT
) were studied in patients with three diagnoses: depressive episode, recurrent depression, and mixed anxiety and depressive disorder. We observed statistically significant differences in the distribution of alleles for the
SLC6A3
(
DAT1
) 40 bp VNTR locus in patients with mixed anxiety and depressive disorder. The short allele (
8R
and
9R
) was more common in patients than in the control group (
p
= 0.005); significant differences were also observed in the distribution of genotypes of this locus (
p
= 0.025). No associations were found between the loci of the dopaminergic system and the risk of depressive episode and recurrent depression. Depression is characterized by extremely high clinical heterogeneity. Only a few of the many symptoms of depression may overlap in different people with major depressive disorder. The search for molecular genetic markers of depression often yields conflicting results, which may be due to the heterogeneity of the samples. The aim of this work was to identify genetic risk factors for three diseases characterized by severe depressive symptoms. All participants were of East Slavic origin from Moscow and the regions of Central Russia. The polymorphisms of the genes of the dopamine transporter (SLC6A3/DAT1), dopamine receptors (DRD4 and DRD2), and the enzyme catechol-O-methyltransferase (COMT) were studied in patients with three diagnoses: depressive episode, recurrent depression, and mixed anxiety and depressive disorder. We observed statistically significant differences in the distribution of alleles for the SLC6A3 (DAT1) 40 bp VNTR locus in patients with mixed anxiety and depressive disorder. The short allele (8R and 9R) was more common in patients than in the control group (p = 0.005); significant differences were also observed in the distribution of genotypes of this locus (p = 0.025). No associations were found between the loci of the dopaminergic system and the risk of depressive episode and recurrent depression. |
| Author | Vasilyev, V. A. Slominsky, P. A. Shadrina, M. I. Rafikova, E. I. Shibalev, D. V. Guekht, A. B. Ryskov, A. P. |
| Author_xml | – sequence: 1 givenname: E. I. surname: Rafikova fullname: Rafikova, E. I. email: kat.rafikov@gmail.com organization: Institute of Gene Biology, Russian Academy of Sciences – sequence: 2 givenname: D. V. surname: Shibalev fullname: Shibalev, D. V. organization: Institute of Gene Biology, Russian Academy of Sciences – sequence: 3 givenname: M. I. surname: Shadrina fullname: Shadrina, M. I. organization: Institute of Molecular Genetics, National Research Center Kurchatov Institute – sequence: 4 givenname: P. A. surname: Slominsky fullname: Slominsky, P. A. organization: Institute of Molecular Genetics, National Research Center Kurchatov Institute – sequence: 5 givenname: A. B. surname: Guekht fullname: Guekht, A. B. organization: Moscow Research and Clinical Center for Neuropsychiatry of the Healthcare Department – sequence: 6 givenname: A. P. surname: Ryskov fullname: Ryskov, A. P. organization: Institute of Gene Biology, Russian Academy of Sciences – sequence: 7 givenname: V. A. surname: Vasilyev fullname: Vasilyev, V. A. organization: Institute of Gene Biology, Russian Academy of Sciences |
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| Cites_doi | 10.4088/JCP.12084su1c.01 10.1016/j.brainres.2010.08.064 10.3103/S0891416818030035 10.1016/S0304-3940(02)01125-4 10.1134/S0026893314020174 10.1038/sj.tpj.6500208 10.1002/wps.20461 10.1186/1471-2156-6-55 10.1016/j.biopsych.2005.01.030 10.1016/j.biopsych.2004.08.008 10.1038/sj.mp.4000921 10.1001/archpsyc.1991.01810310066012 10.1016/j.jad.2014.01.015 10.1038/sj.tpj.6500026 10.1016/j.jad.2010.11.012 10.2147/NDT.S138565 10.1097/00008571-199606000-00007 10.1111/ahg.12263 10.3109/15622975.2015.1083615 |
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| Copyright | Pleiades Publishing, Inc. 2021. ISSN 1022-7954, Russian Journal of Genetics, 2021, Vol. 57, No. 8, pp. 942–948. © Pleiades Publishing, Inc., 2021. Russian Text © The Author(s), 2021, published in Genetika, 2021, Vol. 57, No. 8, pp. 941–948. |
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| References | Zhang, L., Hu, L., Li, X., et al., The DRD2 rs1800497 polymorphism increase the risk of mood disorder: evidence from an update meta-analysis, J. Affect. Disord., 2014, no. 158, pp. 71—77. https://doi.org/10.1016/j.jad.2014.01.015 Inoue-MurayamaM.AdachiaS.MishimaN.Variation of variable number of tandem repeat sequences in the 3'-untranslated region of primate dopamine transporter genes that affects reporter gene expressionNeurosci. Lett.20023342062101:CAS:528:DC%2BD38XovFGls78%3D10.1016/S0304-3940(02)01125-412453630 NobleE.P.BlumK.RitchieT.Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholismArch. Gen. Psychiatry1991486486541:STN:280:DyaK3M3pvVyntg%3D%3D10.1001/archpsyc.1991.018103100660122069496 FehretdinovaD.I.SukhodolskayaE.M.ShibalevD.V.Polymorphism of the two genes encoding catecholamine degradation enzymes (COMT and MAOA) in the Hadza and Datoga African ethnic populationsMol. Genet., Microbiol. Virol.20183319520010.3103/S0891416818030035 LachmanH.M.PapolosD.F.SaitoT.Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disordersPharmacogenetics199662432501:CAS:528:DyaK28XksFemsLw%3D10.1097/00008571-199606000-00007 KleinM.SchmoegerM.KasperS.SchosseA.Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of genderWorld J. Biol. Psychiatry20161714715810.3109/15622975.2015.108361526813412 Bielinski, M., Jaracz, M., Lesiewska, N., et al., Association between COMT Val158Met and DAT1 polymorphisms and depressive symptoms in the obese population, Neuropsychiatr. Dis. Treat., 2017, no. 13, pp. 2221—2229. https://doi.org/10.2147/NDT.S138565 Thase, M.E., The multifactorial presentation of depression in acute care, J. Clin. Psychiatry, 2013, no. 74, suppl. 2, pp. 3—8. https://doi.org/10.4088/JCP.12084su1c.01 FukeS.SuoS.TakahashiN.The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expressionPharmacogenomics J.200111521561:CAS:528:DC%2BD3MXnt1elu7g%3D10.1038/sj.tpj.650002611911442 SukhodolskayaE.M.FehretdinovaD.I.ShibalevD.V.Polymorphisms of dopamine receptor genes DRD2 and DRD4 in African populations of Hadza and Datoga differing in the level of culturally permitted aggressionAnn. Hum. Genet.2018824074141:CAS:528:DC%2BC1cXhvFeqsbrE10.1111/ahg.1226330009502 D’SouzaU.M.RussaC.TahiretE.Functional effects of a tandem duplication polymorphism in the 5'flanking region of the DRD4 geneBiol. Psychiatry2004566916971:CAS:528:DC%2BD2cXptFOmt7o%3D10.1016/j.biopsych.2004.08.00815522254 Sukhodol’skayaE.M.Vasil’evV.A.ShibalevD.V.3′-UTR polymorphism of dopamine transporter gene in Hadza and Datoga malesMol. Biol. (Moscow)2014482542571:CAS:528:DC%2BC2cXntFGgtro%3D10.1134/S0026893314020174 Lopez LeonS.CroesaE.A.Sayed-TabatabaeiF.A.The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: a meta-analysisBiol. Psychiatry20055799910031:CAS:528:DC%2BD2MXjslKhtrg%3D10.1016/j.biopsych.2005.01.03015860340 KessingL.V.BukhJ.D.The clinical relevance of qualitatively distinct subtypes of depressionWorld Psychiatry20171631831910.1002/wps.20461289411125608844 SchootsO.Van TolH.H.The human dopamine D4 receptor repeat sequences modulate expressionPharmacogenomics J.200333433481:CAS:528:DC%2BD3sXps1yiur4%3D10.1038/sj.tpj.650020814581929 MillerG.M.MadrasB.K.Polymorphisms in the 3'-untranslated region of human and monkey dopamine transporter genes affect reporter gene expressionMol. Psychiatry2002744551:CAS:528:DC%2BD38XhsVGmu7o%3D10.1038/sj.mp.400092111803445 VanNess, S.H., Owens, M.J., and Kilts, C.D., The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density, BMC Genet., 2005, no. 6, p. 55. https://doi.org/10.1186/1471-2156-6-55 Lai, J.H., Zhuab, Y.S., Huoet, Z.H., et al., Association study of polymorphisms in the promoter region of DRD4 with schizophrenia, depression, and heroin addiction, Brain Res., 2010, no. 1359, pp. 227—232. https://doi.org/10.1016/j.brainres.2010.08.064 ZouY.F.WangF.FengetX.L.Association of DRD2 gene polymorphisms with mood disorders: a meta-analysisJ. Affect. Disord.20121362292371:CAS:528:DC%2BC38XisFWmsbg%3D10.1016/j.jad.2010.11.01221130502 1488_CR7 1488_CR6 O. Schoots (1488_CR9) 2003; 3 L.V. Kessing (1488_CR2) 2017; 16 1488_CR1 D.I. Fehretdinova (1488_CR18) 2018; 33 S. Lopez Leon (1488_CR10) 2005; 57 H.M. Lachman (1488_CR15) 1996; 6 U.M. D’Souza (1488_CR8) 2004; 56 E.P. Noble (1488_CR12) 1991; 48 E.M. Sukhodolskaya (1488_CR17) 2018; 82 1488_CR14 1488_CR11 G.M. Miller (1488_CR3) 2002; 7 Y.F. Zou (1488_CR13) 2012; 136 E.M. Sukhodol’skaya (1488_CR19) 2014; 48 S. Fuke (1488_CR4) 2001; 1 M. Klein (1488_CR16) 2016; 17 M. Inoue-Murayama (1488_CR5) 2002; 334 |
| References_xml | – reference: Bielinski, M., Jaracz, M., Lesiewska, N., et al., Association between COMT Val158Met and DAT1 polymorphisms and depressive symptoms in the obese population, Neuropsychiatr. Dis. Treat., 2017, no. 13, pp. 2221—2229. https://doi.org/10.2147/NDT.S138565 – reference: Zhang, L., Hu, L., Li, X., et al., The DRD2 rs1800497 polymorphism increase the risk of mood disorder: evidence from an update meta-analysis, J. Affect. Disord., 2014, no. 158, pp. 71—77. https://doi.org/10.1016/j.jad.2014.01.015 – reference: SukhodolskayaE.M.FehretdinovaD.I.ShibalevD.V.Polymorphisms of dopamine receptor genes DRD2 and DRD4 in African populations of Hadza and Datoga differing in the level of culturally permitted aggressionAnn. Hum. Genet.2018824074141:CAS:528:DC%2BC1cXhvFeqsbrE10.1111/ahg.1226330009502 – reference: D’SouzaU.M.RussaC.TahiretE.Functional effects of a tandem duplication polymorphism in the 5'flanking region of the DRD4 geneBiol. Psychiatry2004566916971:CAS:528:DC%2BD2cXptFOmt7o%3D10.1016/j.biopsych.2004.08.00815522254 – reference: FehretdinovaD.I.SukhodolskayaE.M.ShibalevD.V.Polymorphism of the two genes encoding catecholamine degradation enzymes (COMT and MAOA) in the Hadza and Datoga African ethnic populationsMol. Genet., Microbiol. Virol.20183319520010.3103/S0891416818030035 – reference: MillerG.M.MadrasB.K.Polymorphisms in the 3'-untranslated region of human and monkey dopamine transporter genes affect reporter gene expressionMol. Psychiatry2002744551:CAS:528:DC%2BD38XhsVGmu7o%3D10.1038/sj.mp.400092111803445 – reference: Thase, M.E., The multifactorial presentation of depression in acute care, J. Clin. Psychiatry, 2013, no. 74, suppl. 2, pp. 3—8. https://doi.org/10.4088/JCP.12084su1c.01 – reference: FukeS.SuoS.TakahashiN.The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expressionPharmacogenomics J.200111521561:CAS:528:DC%2BD3MXnt1elu7g%3D10.1038/sj.tpj.650002611911442 – reference: Sukhodol’skayaE.M.Vasil’evV.A.ShibalevD.V.3′-UTR polymorphism of dopamine transporter gene in Hadza and Datoga malesMol. Biol. (Moscow)2014482542571:CAS:528:DC%2BC2cXntFGgtro%3D10.1134/S0026893314020174 – reference: NobleE.P.BlumK.RitchieT.Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholismArch. Gen. Psychiatry1991486486541:STN:280:DyaK3M3pvVyntg%3D%3D10.1001/archpsyc.1991.018103100660122069496 – reference: Inoue-MurayamaM.AdachiaS.MishimaN.Variation of variable number of tandem repeat sequences in the 3'-untranslated region of primate dopamine transporter genes that affects reporter gene expressionNeurosci. Lett.20023342062101:CAS:528:DC%2BD38XovFGls78%3D10.1016/S0304-3940(02)01125-412453630 – reference: KessingL.V.BukhJ.D.The clinical relevance of qualitatively distinct subtypes of depressionWorld Psychiatry20171631831910.1002/wps.20461289411125608844 – reference: SchootsO.Van TolH.H.The human dopamine D4 receptor repeat sequences modulate expressionPharmacogenomics J.200333433481:CAS:528:DC%2BD3sXps1yiur4%3D10.1038/sj.tpj.650020814581929 – reference: Lopez LeonS.CroesaE.A.Sayed-TabatabaeiF.A.The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: a meta-analysisBiol. Psychiatry20055799910031:CAS:528:DC%2BD2MXjslKhtrg%3D10.1016/j.biopsych.2005.01.03015860340 – reference: ZouY.F.WangF.FengetX.L.Association of DRD2 gene polymorphisms with mood disorders: a meta-analysisJ. Affect. Disord.20121362292371:CAS:528:DC%2BC38XisFWmsbg%3D10.1016/j.jad.2010.11.01221130502 – reference: Lai, J.H., Zhuab, Y.S., Huoet, Z.H., et al., Association study of polymorphisms in the promoter region of DRD4 with schizophrenia, depression, and heroin addiction, Brain Res., 2010, no. 1359, pp. 227—232. https://doi.org/10.1016/j.brainres.2010.08.064 – reference: KleinM.SchmoegerM.KasperS.SchosseA.Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of genderWorld J. Biol. 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| Title | Influence of Polymorphic Gene Variants of the Dopaminergic System on the Risk of Disorders with Depressive Symptoms |
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