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
Department of Psychiatry, Korea University, College of Medicine, Seoul, Republic of Korea.
Department of Psychiatry, Gangnam Eulji Hospital, Eulji University, Seoul, Republic of Korea.
J Affect Disord. 2014 Apr;158:127-32. doi: 10.1016/j.jad.2014.01.018. Epub 2014 Feb 11.
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.
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.
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.
Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations.
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.
尽管有多项研究调查了去甲肾上腺素神经递质转运体基因（SLC6A2）多态性与抑郁症之间可能存在的关联，但很少有研究探讨SLC6A2多态性与自杀之间的关联。
对550名患者检测了三个单核苷酸多态性（rs2242446、rs28386840和rs5569）：201名有自杀未遂的重度抑郁症（MDD）患者、160名无自杀未遂的MDD患者和189名健康对照者。对三组进行单核苷酸多态性（SNP）和单倍型分析。随后，进行了调整年龄和性别的多因素逻辑回归分析，以确定每个SNP的独立影响。还研究了自杀致死性与SLC6A2多态性之间可能存在的关联。
在基因型和等位基因频率分析中，自杀性MDD患者与健康对照者之间的rs28386840存在显著差异。在单倍型分析中，TAA（rs2242446-rs28386840-rs5569，从左至右）与MDD患者的自杀未遂相关，尽管在Bonferroni校正后显著性（p=0.043）消失。自杀性MDD患者的致死性评分与SLC6A2多态性之间无关联。
样本量适中以及仅分析了单一类型的神经递质（去甲肾上腺素）是主要局限性。
我们的结果表明，SLC6A2多态性与MDD患者的自杀风险相关。未来有必要开展研究以阐明SLC6A2多态性影响自杀风险的可能机制。
