Zinc transporter-3 [SLC30A3 (rs11126936)] polymorphism is associated with major depressive disorder in Asian subjects

Abstract

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.

Predictors of recurrence of major depressive disorder

“…The original study was a case-control study in which the methodology has been described elsewhere [33]. Inclusion criteria included male and female patients from 18 to 65 years of age, who were diagnosed with single or recurrent, non-psychotic episode of Major Depressive Disorder (using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [1]) diagnosed less than 2 years prior to recruitment.…”

“…Primers (both sense and antisense) were used to amplify the targeted single nucleotide polymorphisms (SNPs) namely, BsmI +63980 G>A (rs1544410), ApaI +-64978C>A (rs7975232) and TaqI +65058 T>C (rs731236) in the Vitamin D Receptor (VDR) gene, SLC30A3 rs11126396 of ZnT3 gene, rs40184 C>T of Dopamine Transporter-1 (DAT1) gene, rs6265 G196A of Brain-derived neurotropic factor (BDNF) gene, rs6295 -1019C>G of serotonin receptor 1A(HT1A) gene, and rs6311 -1438A>G of serotonin receptor 2A (HT2A) gene. Details of the genotyping methods have been fully described elsewhere [33,42] and in S2 Appendix and S3 Appendix.…”

“…Mutations in the brain-derived neurotropic factor (BDNF) [29,30] and serotonin receptor genes [31] were shown to be associated with recurrent MDD. In addition, findings by Kuningas et al (2009) [32] and Lye et al [33] that single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) and zinc transporter-3 (SLC30A3) genes were respectively associated with MDD, and together with evidence that SNPs of dopamine transporter-1 gene increased risk of MDD [34,35], led to renewed interest in determining if an association exists between VDR, ZnT3 SNPs and recurrence of MDD.…”

Variants in the zinc transporter-3 encoding gene (SLC30A3) in schizophrenia and bipolar disorder: Effects on brain glutamate–A pilot study

“…A meta-analysis of 14 samples of European descent (total N = 18,826), including data from genome-wide association studies (GWAS), confirmed the associations of rs11126936 and rs11126929, where the minor alleles were again significantly overrepresented in females with schizophrenia ( 14 ). In contrast, a polymorphism of the SLC30A3 gene (rs11126936) has been shown to be associated with major depressive disorder in a cohort of Asian participants, with those homozygous for the minor allele having reduced risk of MDD ( 16 ).…”

Research beyond biomedical confines: towards better mental health and well-being for all

“…Individuals with a mental disorder have a nearly eightfold increased risk of suicide compared with those without a mental disorder; hence, the risk these conditions present should not be downplayed [4]. Nonetheless, our review of NeurosciRN publications over the past two years has found only three articles to date, which focused specifically on mental disorders, namely dementia [5], bipolar disorder [6], and major depressive disorder [7] . Thus, it may not be a surprise for the majority of both researchers and the readership to question when confronted with this editorial: 'Why should I be concerned about considering the aspect of mental health to address suicide risk and if so how could I then contribute towards suicide prevention through research, discussion and promotion of mental health and well-being?…”