Association between a Missense Polymorphism (rs3924999, Arg253Gln) of Neuregulin 1 and Schizophrenia in Korean Population

다국어 초록 (Multilingual Abstract)

Neuregulin 1 (NRG1) is associated with the pathogenesis of schizophrenia through controlling activation and signaling of neurotransmitter receptors. Influence to schizophrenia development by the NRG1 gene may differ in individuals, and genetic polymorphism is one of the factors affecting their differences. Association between three single nucleotide polymorphisms (SNPs) (rs7014762, -1174 A/T; rs11998176, -788 A/T; rs3924999, Arg253Gln) of NRG1 and the development of schizophrenia was analyzed in 221 schizophrneia and 359 control subjects. Polymerase chain reaction and direct sequencing were performed to obtain genotype data of NRG1 SNPs of the subjects. In analysis of genetic data, multiple logistic regression models (codominant1, codominant2, dominant, recessive, and log-additive model) were applied. SNPStats and SPSS 18.0 were used to calculate odds ratio (OR), 95% confidence interval (CI), and p-value of each model. The genotype distributions of rs3924999 were associated with schizophrenia development (OR=0.67, 95% CI=0.47-0.95, p=0.022 in the dominant model and OR=0.69, 95% CI=0.51-0.93, p=0.013 in the log-addtive model) and allelic distributions also showed significant association (OR=0.70, 95% CI=0.52-0.93, p=0.014). The results suggest that rs3924999 of the NRG1 gene may be associated with schizophrenia susceptibility.

참고문헌 (Reference)

1 Hancock ML, "Type III neuregulin 1 regulates pathfinding of sensory axons in the developing spinal cord and periphery" 138 : 4887-4898, 2011

2 Houthoofd S, "Trait and state aspects of internal and external performance monitoring in schizophrenia" 2012

3 Georgieva L, "Support for neuregulin 1 as a susceptibility gene for bipolar disorder and schizophrenia" 64 : 419-427, 2008

4 Quednow BB, "Sensorimotor gating depends on polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase, but not on neuregulin-1 Arg38Gln genotype: a replication study" 66 : 614-620, 2009

5 Anderson G, "Schizophrenia: Linking prenatal infection to cytokines, the tryptophan catabolite (TRYCAT) pathway, NMDA receptor hypofunction, neurodevelopment and neuroprogression" 2012

6 Pitcher GM, "Schizophrenia susceptibility pathway neuregulin 1-ErbB4 suppresses Src upregulation of NMDA receptors" 17 : 470-478, 2011

7 Woo RS, "Neuregulin-1 enhances depolarization-induced GABA release" 54 : 599-610, 2007

8 Stefansson H, "Neuregulin 1 and susceptibility to schizophrenia" 71 : 877-892, 2002

9 Meyer D, "Isoform-specific expression and function of neuregulin" 124 : 3575-3586, 1997

10 Holmes WE, "Identification of heregulin, a specific activator of p185ErbB2" 256 : 1205-1210, 1992

11 Li T, "Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype" 9 : 698-704, 2004

12 Hong LE, "Evidence of missense mutations on the neuregulin 1gene affecting function of prepulse inhibition" 63 : 17-23, 2008

13 Yang JZ, "Association study of neuregulin 1 gene with schizophrenia" 8 : 706-709, 2003

14 Kang C, "Association study of neuregulin 1 gene polymorphisms with auditory P300 in schizophrenia" 159B : 422-428, 2012

15 Stefansson H, "Association of neuregulin 1 with schizophrenia confirmed in a Scottish population" 72 : 83-87, 2003

16 Walker RM, "Association analysis of neuregulin 1 candidate regions in schizophrenia and bipolar disorder" 478 : 9-13, 2010

17 Ah Rang Cho, "Assessment between Dopamine Receptor D2 (DRD2) Polymorphisms and Schizophrenia in Korean Population" 대한정신약물학회 10 (10): 88-93, 2012

18 Pan B, "Antipsychotic treatment and neuregulin 1-ErbB4 signalling in schizophrenia" 35 : 924-930, 2011

19 Hahn CG, "Altered neuregulin 1-ErbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia" 12 : 824-828, 2006

20 Inta D, "Alterations in postnatal neurogenesis and dopamine dysregulation in schizophrenia: a hypothesis" 37 : 674-680, 2011