Association of dopamine receptor D2 -141C insertion/deletion and dopamine beta-hydroxylase 19 bp insertion/deletion polymorphisms with schizophrenia: A case-control study in the eastern Algerian population
DOI:
https://doi.org/10.2298/ABS240526023BKeywords:
dopamine, genetic polymorphisms, DRD2, DBH, schizophreniaAbstract
Paper description:
- The genes that encode for different proteins in the dopaminergic pathway have been implicated in the pathogenesis of schizophrenia.
- Two functional genetic polymorphisms, rs1799732 of the dopamine D2 receptor gene and rs72393728 of the dopamine beta-hydroxylase gene have been investigated for their potential involvement in the susceptibility to schizophrenia in a case-control study.
- The DRD2 rs1799732 polymorphism Del allele was associated with an increased risk for schizophrenia in an Algerian cohort.
- This study provides an improved understanding of genotype and allele distributions of the DRD2 and DBH polymorphisms in the Eastern Algerian population.
Abstract: Numerous studies emphasize genetic contributions to schizophrenia, particularly focusing on genes coding for proteins in the dopaminergic pathway, which are extensively studied for their involvement in the disorder’s pathophysiology. This investigation aimed to examine the potential association between the dopamine receptor D2 (DRD2) -141C insertion/deletion (rs1799732) and the dopamine beta-hydroxylase (DBH) 19 bp insertion/deletion (rs72393728) polymorphisms with schizophrenia in an eastern Algerian population. A case-control study was conducted, involving 145 patients and 146 healthy controls. DNA samples were extracted from peripheral blood cells using the salting out technique. Genotyping for the DRD2 rs1799732 polymorphism was performed using the PCR-RFLP method, while the DBH rs72393728 polymorphism was analyzed using the PCR method. The results revealed a significant association between the DRD2 rs1799732 polymorphism and schizophrenia, evidenced by significant differences in genotypic and allelic distributions between patients and controls (P=0.001 and P=0.001, respectively). However, no statistical differences were found for the DBH rs72393728 polymorphism between patients and controls for genotype (P=0.46) or allele frequencies (P=0.73). This study supports an association between DRD2 rs1799732 polymorphism and schizophrenia in this population while finding no such association with DBH rs72393728 polymorphism. However, there may be a potential interaction between both polymorphisms.
Downloads
References
Mcguffin P, Owen MJ. Genetic basis of schizophrenia. Lancet. 1995;346(8976):678‑82. https://doi.org/1016/s0140-6736(95)92285-7
Pearlson GD, Barta PE, Powers RE, Menon RR, Richards SS, Aylward EH, Federman EB, Chase GA, Petty RG, Tien AY.. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol Psychiatry. 1997;41(1):1‑14. https://doi.org/10.1016/S0006-3223(96)00373-3
Benharrats SS, Bencharif MA. Comorbidity schizophrenia and diabetes mellitus in Algeria – A study of risk factors. Rev Epidemiol Sante Publique. 2019;67(3):189‑97. https://doi.org/10.1016/j.respe.2019.02.005
Hussain MS, Siddiqui SA, Mondal S, Millat MS, Marzan S, Uddin MG, Aziz MA, Alam MF, Islam MS. Association of DRD2 gene polymorphisms with schizophrenia in the young Bangladeshi population: A pilot study. Heliyon. 2020;6(10):e05125. https://doi.org/10.1016/j.heliyon.2020.e05125
Cordeiro Q, Siqueira-Roberto J, Zung S, Vallada H. Association between the DRD2-141C Insertion/Deletion polymorphism and schizophrenia. Arq Neuro-Psiquiatr. 2009;67:191‑4. https://doi.org/10.1590/s0004-282x2009000200004
Sáiz PA, García-Portilla MP, Arango C, Morales B, Arias B, Corcoran P, Fernández JM, Alvarez V, Coto E, Bascarán MT, Bousoño M, Fañanas L, Bobes J. Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: Data from an association study. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(1):26‑31. https://doi.org/10.1016/j.pnpbp.2009.09.008
Xiao L, Shen T, Peng D hui, Shu C, Jiang K da, Wang G hua. Functional −141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter and schizophrenia in a Chinese Han population. J Int Med Res. 2013;41(4):1171‑8. https://doi.org/10.1177/0300060513483415
Seeman P. Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse. 1987;1(2):133‑52. https://doi.org/10.1002/syn.890010203
Kurt H, Dikmen M, Basaran A, Yenilmez C, Ozdemir F, Degirmenci I, Gunes HV, Kucuk MU, Mutlu F. Dopamine D2 receptor gene −141C Insertion/Deletion polymorphism in Turkish schizophrenic patients. Mol Biol Rep. 2011;38(2):1407‑11. https://doi.org/10.1007/s11033-010-0244-6
Jönsson EG, Sillén A, Vares M, Ekholm B, Terenius L, Sedvall GC. Dopamine D2 receptor gene Ser311Cys variant and schizophrenia: association study and meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2003;119B(1):28‑34. https://doi.org/10.1002/ajmg.b.20004
Bulayeva KB, Glatt SJ, Bulayev OA, Pavlova TA, Tsuang MT. Genome-wide linkage scan of schizophrenia: A cross-isolate study. Genomics. 2007;89(2):167‑77. https://doi.org/10.1016/j.ygeno.2006.10.001
Parsons MJ, Mata I, Beperet M, Iribarren-Iriso F, Arroyo B, Sainz R, Arranz MJ, Kerwin R. A dopamine D2 receptor gene-related polymorphism is associated with schizophrenia in a Spanish population isolate. Psychiatr Genet. 2007;17(3):159. https://doi.org/10.1097/YPG.0b013e328017f8a4
Arinami T, Gao M, Hamaguchi H, Toru M. A Functional Polymorphism in the Promoter Region of the Dopamine D2 Receptor Gene Is Associated with Schizophrenia. Hum Mol Genet. 1997;6(4):577‑82. https://doi.org/10.1093/hmg/6.4.577
Breen G, Brown J, Maude S, Fox H, Collier D, Li T, Arranz M, Shaw D, StClair D. −141 C Del/Ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population. Am J Med Genet. 1999;88(4):407‑10. https://doi.org/10.1002/(sici)1096-8628(19990820)88:4<407::aid-ajmg19>3.0.co;2-3
Kampman O, Anttila S, Illi A, Lehtimäki T, M. Mattila K, Roivas M, Leinonen E. Dopamine receptor D2 −141C Insertion/Deletion polymorphism in a Finnish population with schizophrenia. Psychiatry Res. 2003;121(1):89‑92. https://doi.org/10.1016/s0165-1781(03)00201-4
Nunes FDD, Pinto JAF, Freitas PHB, Santos LL, Machado RM. Research Article Frequency of ANKK1, DRD2, DRD3 gene polymorphisms in refractory schizophrenia patients. Genet Mol Res. 2019;18(4):gmr18389. https://doi.org/10.4238/gmr18389
Luu SU, Liao HM, Hung TW, Liu BY, Cheng MC, Liao DL, Chen SJ, Chen CH.. Mutation analysis of adenosine A2a receptor gene and interaction study with dopamine D2 receptor gene in schizophrenia. Psychiatr Genet. 2008;18(1):43. https://doi.org/10.1097/YPG.0b013e3281b1173c
Dubertret C, Bardel C, Ramoz N, Martin PM, Deybach JC, Adès J, Gorwood P, Gouya L. A genetic schizophrenia-susceptibility region located between the ANKK1 and DRD2 genes. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(3):492–9. https://doi.org/10.1016/j.pnpbp.2010.02.003
Zhang X cen, Ding M, Adnan A, Liu Y, Liu Y ping, Xing J xin, Xuan J feng, Xia X, Yao J, Wang B jie. No association between polymorphisms in the promoter region of dopamine receptor D2 gene and schizophrenia in the northern Chinese Han population: A case–control study. Brain Behav. 2019;9(2):e01193. https://doi.org/10.1002/brb3.1193
Ishiguro H, Kim KT, Joh TH, Kim KS. Neuron-specific expression of the human dopamine beta-hydroxylase gene requires both the cAMP-response element and a silencer region. J Biol Chem.. 1993;268(24):17987‑94. https://doi.org/10.1016/S0021-9258(17)46802-5
Cubells JF, van Kammen DP, Kelley ME, Anderson GM, O’Connor DT, Price LH, Malison R, Rao PA, Kobayashi K, Nagatsu T, Gelernter J. Dopamine β-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation. Hum Genet. 1998;102(5):533‑40. https://doi.org/10.1007/s004390050736
Dunnette J, Weinshilboum R. Human serum dopamine beta-hydroxylase: correlation of enzymatic activity with immunoreactive protein in genetically defined samples. Am J Hum Genet. 1976;28(2):155‑66. PMCID: PMC1684916
Cubells JF, Sun X, Li W, Bonsall RW, McGrath JA, Avramopoulos D, Lasseter VK, Wolyniec PS, Tang YL, Mercer K, Pulver AE, Elston RC. Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia. Hum Genet. 2011;130(5):635‑43. https://doi.org/10.1007/s00439-011-0989-6.
Cubells JF, Kranzler HR, McCance-Katz E, Anderson GM, Malison RT, Price LH, Gelernter J. A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry. 2000;5(1):56‑63. https://doi.org/10.1038/sj.mp.4000657
Tang Y lang, Epstein MP, Anderson GM, Zabetian CP, Cubells JF. Genotypic and haplotypic associations of the DBH gene with plasma dopamine β-hydroxylase activity in African Americans. Eur J Hum Genet. 2007;15(8):878‑83. https://doi.org/10.1038/sj.ejhg.5201838
Bell CC. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. JAMA. 1994;272(10):828‑9. https://doi.org/10.1001/jama.1994.03520100096046
Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res. 1988;23(1):99‑110. https://doi.org/10.1016/0165-1781(88)90038-8
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215. https://doi.org/10.1093/nar/16.3.1215
Yamamoto K, Cubells JF, Gelernter J, Benkelfat C, Lalonde P, Bloom D, Lal S, Labelle A, Turecki G, Rouleau GA, Joober R. Dopamine Beta-Hydroxylase (DBH) gene and schizophrenia phenotypic variability: A genetic association study. Am J Med Genet B Neuropsychiatr Genet. 2003;117B(1):33‑8. https://doi.org/10.1002/ajmg.b.10011
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, Sham PC. PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. Am J Hum Genet. 2007;81(3):559‑75. https://doi.org/10.1086/519795
Wang KS, Liu XF, Aragam N. A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. Schizophr Res. 2010;124(1):192‑9 https://doi.org/10.1016/j.schres.2010.09.002
Meira-Lima I, Michelon L, Cordeiro Q, Cho HJ, Vallada H. Allelic association analysis of the functional insertion/deletion polymorphism in the promoter region of the serotonin transporter gene in bipolar affective disorder. J Mol Neurosci. 2005;27(2):219‑24. https://doi.org/10.1385/JMN:27:2:219
Himei A, Koh J, Sakai J, Inada Y, Akabame K, Yoneda H. The influence on the schizophrenic symptoms by the DRD2Ser/Cys311 and −141C Ins/Del polymorphisms. Psychiatry Clin Neurosci. 2002;56(1):97‑102. https://doi.org/10.1046/j.1440-1819.2002.00935.x
Jönsson EG, Nöthen MM, Neidt H, Forslund K, Rylander G, Mattila-Evenden M, Asberg M, Propping P, Sedvall GC. Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia. Schizophr Res. 1999;40(1):31‑6. https://doi.org/10.1016/S0920-9964(99)00033-X
Hori H, Ohmori O, Shinkai T, Kojima H, Nakamura J. Association analysis between two functional dopamine D2 receptor gene polymorphisms and schizophrenia. Am J Med Genet. 2001;105(2):176‑8. https://doi.org/10.1002/ajmg.1196
Shakiba M, Hashemi M, Shahrabadi S, Rezaei M, Taheri M. Lack of Association Between Dopamine Beta-Hydroxylase (DBH) 19-bp Insertion/Deletion Polymorphism and Risk of Schizophrenia. Iran J Psychiatry. 2016;11(4):239‑43. https://doi.org/10.1159/000495238
Zhou N, Yu Q, Li X, Yu Y, Kou C, Li W, Xu H, Luo X, Zuo L, Kosten TR, Zhang X Yang.Association of the dopamine β-hydroxylase 19 bp insertion/deletion polymorphism with positive symptoms but not tardive dyskinesia in schizophrenia. Hum Psychopharmacol: Clin Exp. 2013;28(3):230‑7. https://doi.org/10.1002/hup.2311
Hui L, Zhang X, Huang XF, Han M, Fernandez F, Yu Y, Sun S, Li W, Chen DC, Xiu MH, Kosten TR, Zhang XY. The dopamine b-hydroxylase 19 bp insertion/deletion polymorphism was associated with first-episode but not medicated chronic schizophrenia. J Psychiatr Res. 2012;46(6):733‑7. https://doi.org/10.1016/j.jpsychires.2012.02.016
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Yasmina Boukhenaf, Ouarda Sariayh Ayachi, Rayene Achou, Amina Iness Bernou, Fatima Zohra Madoui, Karima Sifi, Mohamed Larbi Rezgoun
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.
