Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder

Yong Ku Kim, Jung A. Hwang, Heon-Jeong Lee, Ho-Kyoung Yoon, Young-Hoon Ko, Bun Hee Lee, Han Yong Jung, Sang Woo Hahn, Kyoung Sae Na

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Methods Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. Results In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Limitations Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Conclusion Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk.

Original languageEnglish
Pages (from-to)127-132
Number of pages6
JournalJournal of Affective Disorders
Volume158
DOIs
Publication statusPublished - 2014 Apr 1

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Norepinephrine Plasma Membrane Transport Proteins
Major Depressive Disorder
Suicide
Genes
Single Nucleotide Polymorphism
Haplotypes
Neurotransmitter Transport Proteins
Gene Frequency
Sample Size
Neurotransmitter Agents
Norepinephrine
Logistic Models
Genotype
Regression Analysis
Depression

Keywords

  • Depression
  • Single nucleotide polymorphisms
  • SLC6A2
  • Suicide

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder. / Kim, Yong Ku; Hwang, Jung A.; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Ko, Young-Hoon; Lee, Bun Hee; Jung, Han Yong; Hahn, Sang Woo; Na, Kyoung Sae.

In: Journal of Affective Disorders, Vol. 158, 01.04.2014, p. 127-132.

Research output: Contribution to journalArticle

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AU - Ko, Young-Hoon

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N2 - Background Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Methods Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. Results In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Limitations Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Conclusion Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk.

AB - Background Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Methods Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. Results In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Limitations Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Conclusion Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk.

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