Zinc transporter-3 [SLC30A3 (rs11126936)] polymorphism is associated with major depressive disorder in Asian subjects
Major depressive disorder (MDD) compromises the individual’s capacity for self-care and productivity. Single nucleotide polymorphisms (SNP) of a number of genes have been associated with MDD. The zinc transporter-3 protein, encoded by the ZnT3 (SLC30A3) gene, maintains zinc-glutamate homeostasis at the glutamatergic synapse, a disruption of which increases risk of MDD. We hypothesise that variation in SLC30A3 (rs11126936) SNP increases risk of MDD. We recruited 300 MDD cases and 300 controls, matched in the ratio of 1:1 by age, gender and ethnicity. PCR-restriction fragment length polymorphism analysis was used in DNA genotyping, validated by sequencing 10% of samples. Deviation from the Hardy-Weinberg equilibrium was tested using the chi-square test. Conditional logistic regression was used to estimate adjusted odds ratios, controlling for age, gender, ethnicity, occupation and family monthly income. Genotypes G/G and G/T showed two times greater odds of developing MDD compared to variant genotype T/T (OR=1.983, 95% CI=1.031-3.815; p=0.040 and OR=2.232, 95% CI=1.100-4.533; p=0.026 respectively). Carriers of genotypes G/G and G/T of the SNP rs11126936 in SLC30A3 are associated with increased risk of MDD.
Aldoghachi AF, Tor YS, Redzun SZ, Bin Lokman KA, Razaq NAA, Shahbudin AF, et al. Screening of brain-derived neurotrophic factor (BDNF) single nucleotide polymorphisms and plasma BDNF levels among Malaysian major depressive disorder patients. PLoS ONE. 2019;14(1):e0211241. https://doi.org/10.1371/journal.pone.0211241
Avenevoli S, Swendsen J, He J-P, Burstein M, Merikangas KR. Major depression in the national comorbidity survey-adolescent supplement: prevalence, correlates, and treatment. J Am Acad Child Adolesc Psychiatry. 2015;54(1):37-44.e2. https://doi.org/10.1016/j.jaac.2014.10.010
Bierut LJ, Heath AC, Bucholz KK, Dinwiddie SH, Madden PA, Statham DJ, et al. Major depressive disorder in a community-based twin sample: are there different genetic and environmental contributions for men and women? Arch Gen Psychiatry. 1999;56(6):557-563. https://doi.org/10.1001/archpsyc.56.6.557
Bostwick JM, Pankratz VS. Affective disorders and suicide risk: a reexamination. Am J Psychiatry. 2000;157(12):1925-1932. https://doi.org/10.1176/appi.ajp.157.12.1925
Collins PY, Insel TR, Chockalingam A, Daar A, Maddox YT. Grand challenges in global mental health: integration in research, policy, and practice. PLoS Med. 2013;10(4):e1001434. https://doi.org/10.1371/journal.pmed.1001434
Court M. Court Lab Calculator. Available online: https://www.researchgate.net/file.PostFileLoader.html?id=58dbf27a96b7e4fc194da329&assetKey=AS%3A477303651213312%401490809466020. (accessed on 20 April 2018)
Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). Fifth edition. American Psychiatric Publishing, Incorporated; 2013. pp. 991, ISBN: 978-0-89042-554-1.
Fernandez-Pujals AM, Adams MJ, Thomson P, McKechanie AG, Blackwood DHR, Smith BH, et al. Epidemiology and Heritability of Major Depressive Disorder, Stratified by Age of Onset, Sex, and Illness Course in Generation Scotland: Scottish Family Health Study (GS:SFHS). PLoS ONE. 2015;10(11):e0142197. https://doi.org/10.1371/journal.pone.0142197
Frederickson CJ, Suh SW, Silva D, Frederickson CJ, Thompson RB. Importance of zinc in the central nervous system: the zinc-containing neuron. J Nutr. 2000;130(5S Suppl):1471S-1483S. https://doi.org/10.1093/jn/130.5.1471S
Frederickson CJ. Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol. 1989;31:145-238.
Fried EI, Nesse RM. The impact of individual depressive symptoms on impairment of psychosocial functioning. PLoS ONE. 2014;9(2):e90311. https://doi.org/10.1371/journal.pone.0090311
Froud A, Murphy J, Cribb L, Ng CH, Sarris J. The relationship between dietary quality, serum brain-derived neurotrophic factor (BDNF) level, and the Val66met polymorphism in predicting depression. Nutr Neurosci. 2017;22(7):513-521. https://doi.org/10.1080/1028415X.2017.1415281
Fujihara J, Yasuda T, Kimura-Kataoka K, Takinami Y, Nagao M, Takeshita H. Association of SNPs in genes encoding zinc transporters on blood zinc levels in humans. Leg Med (Tokyo). 2018;30(0):28-33. https://doi.org/10.1016/j.legalmed.2017.10.009
Greden JF. The burden of recurrent depression: causes, consequences, and future prospects. J Clin Psychiatry. 2001;62 Suppl 22(suppl 22):5-9.
Hao R, Qi Y, Hou D-N, Ji Y-Y, Zheng C-Y, Li C-Y, et al. BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors. Front Cell Neurosci. 2017;11(1):306. https://doi.org/10.3389/fncel.2017.00306
Hediger MA, Clémençon B, Burrier RE, Bruford EA. The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol Aspects Med. 2013;34(2-3):95-107. https://doi.org/10.1016/j.mam.2012.12.009
Ibrahim N, Sherina MS, Phang CK, Mukhtar F, Awang H, Ang JK, et al. Prevalence and predictors of depression and suicidal ideation among adolescents attending government secondary schools in Malaysia. Med J Malaysia. 2017;72(4):221-227.
Kendler KS, Pedersen NL, Neale MC, Mathé AA. A pilot Swedish twin study of affective illness including hospital- and population-ascertained subsamples: results of model fitting. Behav Genet. 1995;25(3):217-232.
Kendler KS, Prescott CA. A population-based twin study of lifetime major depression in men and women. Arch Gen Psychiatry. 1999;56(1):39-44. https://doi.org/10.1001/archpsyc.56.1.39
Levinson DF, Nichols WE. Major Depression and Genetics - Genetics of Brain Function - Stanford University School of Medicine. Available online: http://med.stanford.edu/depressiongenetics/mddandgenes.html (accessed on 26 June 2018)
Lin Y-MJ, Ko H-C, Chang F-M, Yeh T-L, Sun HS. Population-specific functional variant of the TPH2 gene 2755C>A polymorphism contributes risk association to major depression and anxiety in Chinese peripartum women. Arch Womens Ment Health. 2009;12(6):401-408. https://doi.org/10.1007/s00737-009-0088-z
Maideen SFK, Sidik SM, Rampal L, Mukhtar F. Prevalence, associated factors and predictors of depression among adults in the community of Selangor, Malaysia. PLoS ONE. 2014;9(4):e95395. https://doi.org/10.1371/journal.pone.0095395
McAllister BB, Dyck RH. Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function. Neurosci Biobehav Rev. 2017;80:329-350. https://doi.org/10.1016/j.neubiorev.2017.06.006
McGuffin P, Katz R, Watkins S, Rutherford J. A hospital-based twin register of the heritability of DSM-IV unipolar depression. Arch Gen Psychiatry. 1996;53(2):129-136. https://doi.org/10.1001/archpsyc.1996.01830020047006
McLoughlin IJ, Hodge JS. Zinc in depressive disorder. Acta Psychiatr Scand. 1990;82(6):451-453. https://doi.org/10.1111/j.1600-0447.1990.tb03077.x
Mlyniec K. Zinc in the Glutamatergic Theory of Depression. Curr Neuropharmacol. 2015;13(4):505-513.
Nagaraj S. Intermarriage in Malaysia. Malays J Econ Stud. 2009;46(1):75-92.
National Center for Biotechnology Information. Reference SNP (refSNP) Cluster Report: rs11126936. Availabel online: https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs11126936. (accessed on 12 July 2018)
Paoletti P, Vergnano AM, Barbour B, Casado M. Zinc at glutamatergic synapses. Neuroscience. 2008;158(1):126-136. https://doi.org/10.1016/j.neuroscience.2008.01.061
Patten SB, Williams JVA, Lavorato DH, Wang JL, McDonald K, Bulloch AGM. Descriptive epidemiology of major depressive disorder in Canada in 2012. Can J Psychiatry. 2015;60(1):23-30. https://doi.org/10.1177/070674371506000106
Perez-Becerril C, Morris AG, Mortimer A, McKenna PJ, de Belleroche J. Allelic variants in the zinc transporter-3 gene, SLC30A3, a candidate gene identified from gene expression studies, show gender-specific association with schizophrenia. Psychiatry. 2014;29(3):172-178. https://doi.org/10.1016/j.eurpsy.2013.05.007
Petrilli MA, Kranz TM, Kleinhaus K, Joe P, Getz M, Johnson P, et al. The Emerging Role for Zinc in Depression and Psychosis. Front Pharmacol. 2017;8:414. https://doi.org/10.3389/fphar.2017.00414
Sidik SM, Arroll B, Goodyear F. Prevalence of depression among women attending a primary urban care clinic in Malaysia. Singapore Med J. 2012;53:468-473.
Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000;157(10):1552-1562. https://doi.org/10.1176/appi.ajp.157.10.1552
Sund AM, Larsson B, Wichstrøm L. Prevalence and characteristics of depressive disorders in early adolescents in central Norway. Child Adolesc Psychiatry Ment Health. 2011;5:28. https://doi.org/10.1186/1753-2000-5-28
Tan KL, Yadav H. Depression among the urban poor in Peninsular Malaysia: a community based cross-sectional study. J Health Psychol. 2012;18(1):121-127. https://doi.org/10.1177/1359105311433908
Turner S, Armstrong LL, Bradford Y, Carlson CS, Crawford DC, Crenshaw AT, et al. Quality control procedures for genome-wide association studies. Curr Protoc Hum Genet. 2011;Chapter 1:Unit1.19. https://doi.org/10.1002/0471142905.hg0119s68
Wigner P, Czarny P, Synowiec E, Bijak M, Białek K, Talarowska M, et al. Association between single nucleotide polymorphisms of TPH1 and TPH2 genes, and depressive disorders. J Cell Mol Med. 2018;22(3):1778-1791. https://doi.org/10.1111/jcmm.13459
World Health Organization. Depression and other common mental disorders: global health estimates. 2017.
Xiao Z, Liu W, Gao K, Wan Q, Yang C, Wang H, et al. Interaction between CRHR1 and BDNF genes increases the risk of recurrent major depressive disorder in Chinese population. PLoS ONE. 2011;6(12):e28733. https://doi.org/10.1371/journal.pone.0028733
Yee WS, Lin LP. Anxiety and depressive symptoms among communities in the east coast of Peninsular Malaysia: A rural exploration. Malays J Psychiatry. 2011;20(1).
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