Lack of association to a NRG1 missense polymorphism in schizophrenia or bipolar disorder in a Costa Rican population

SCHIZOPHRENIA RESEARCH

卷:131

Article

Moon, Emily¹  Rollins, Brandi¹  Mesen, Andrea²  Sequeira, Adolfo¹  Myers, Richard M.³  Akil, Huda⁴  Watson, Stanley J.⁴  Barchas, Jack⁵  Jones, Edward G.⁶  Schatzberg, Alan⁷  Bunney, William E.¹  DeLisi, Lynn E.⁸  Byerley, William⁹  Vawter, Marquis P.¹ 

[1] Univ Calif Irvine, Dept Psychiat & Human Behav, Sch Med, Irvine, CA 92717 USA

[2] Ctr Neuropsychiat Studies Costa Rica, ACENP Costa Rica, San Jose, Costa Rica

[3] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

[4] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA

[5] Cornell Univ, Dept Psychiat, New York, NY 10021 USA

[6] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA

[7] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA

[8] Boston VA, Dept Psychiat, Brockton, MA USA

[9] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA

关键词: Neuregulin 1 isoform expression;    Schizophrenia;    Isolated population;    Costa Rica;    Bipolar disorder;    Major depressive disorder;    Hippocampus;    Dorsolateral prefrontal cortex;   

DOI  :  10.1016/j.schres.2011.06.024

来源: Elsevier

【 摘 要 】

A missense polymorphism in the NRG1 gene, Val>Leu in exon 11, was reported to increase the risk of schizophrenia in selected families from the Central Valley region of Costa Rica (CVCR). The present study investigated the relationship between three NRG1 genetic variants, rs6994992, rs3924999, and Val>Leu missense polymorphism in exon 11, in cases and selected controls from an isolated population from the CVCR. Isolated populations can have less genetic heterogeneity and increase power to detect risk variants in candidate genes. Subjects with bipolar disorder (BD, n = 358), schizophrenia (SZ, n = 273), or unrelated controls (CO, n = 479) were genotyped for three NRG1 variants. The NRG1 promoter polymorphism (rs6994992) was related to altered expression of NRG1 Type IV in other studies. The expression of NRG1 type IV in the dorsolateral prefrontal cortex (DLPFC) and the effect of the rs6994992 genotype on expression were explored in a postmortem cohort of BD. SZ, major depressive disorder (MOD) cases, and controls. The missense polymorphism Val>Leu in exon 11 was not significantly associated with schizophrenia as previously reported in a family sample from this population, the minor allele frequency is 4%, thus our sample size is not large enough to detect an association. We observed however an association of rs6994992 with NRG1 type IV expression in DLPFC and a significantly decreased expression in MDD compared to controls. The present results while negative do not rule out a genetic association of these SNPs with BD and SZ in CVCR, perhaps due to small risk effects that we were unable to detect and potential intergenic epistasis. The previous genetic relationship between expression of a putative brain-specific isoform of NRG1 type IV and SNP variation was replicated in postmortem samples in our preliminary study. (C) 2011 Elsevier B.V. All rights reserved.

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