Association between genetic variants of the norepinephrine transporter gene (SLC6A2) and bipolar I disorder

Sun Young Kim, Han Na Kim, Sang Won Jeon, Weon Jeong Lim, Soo In Kim, Youn Jung Lee, Se Young Kim, Yong Ku Kim

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3 Scopus citations

Abstract

We aimed to investigate the associations between genetic variants of the norepinephrine transporter gene (NET, also known as SLC6A2) and diagnosis of bipolar I disorder. In addition, we examined the relationship between the genetic variants and manic and psychotic symptoms in patients with bipolar I disorder. The three SNPs rs28386840, rs2242446, and rs5569 were genotyped in 326 patients: patients with bipolar I disorder (n = 160) and a control group (n = 166). Subsequently, multivariate logistic regression analysis adjusting for age and sex was conducted to identify independent influences of the SNPs on diagnosis of bipolar I disorder. A possible association between manic and psychotic symptoms and variants of SLC6A2 was also investigated in patients with bipolar I disorder. The rs28836840 SNP in the 5’-UTR of SLC6A2 was significantly associated with bipolar I disorder and with severity of manic and psychotic symptoms in this disorder. Individuals carrying a T allele in the rs28836840 SNP were likely to have a lower risk of bipolar I disorder or lower severity of manic and psychotic symptoms in patients with bipolar I disorder (bipolar I disorder diagnosis: OR = 0.643, 95% Cl = 0.468–0.883, p = 0.006; manic symptoms: β = −2.457, 95% Cl = −4.674 ~ −0.239, p = 0.031; psychotic symptoms: β = −2.501, 95% Cl = −4.700 ~ −0.301, p = 0.027). For the rs2242446 and rs5569 SNPs, there were no significant differences between patients with bipolar I disorder and those without. Our results revealed associations of the rs28386840 SNP with bipolar I disorder diagnosis and with severity of manic and psychotic symptoms. However, the findings reported here require replication in larger samples and various ethnic groups.

Original languageEnglish
Article number110227
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume107
DOIs
StatePublished - 20 Apr 2021

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • Bipolar I disorder
  • Manic symptom
  • NET
  • Psychotic symptom
  • SLC6A2

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